Mitochondria and Brain Disorders

Mitochondria and Brain Disorders
Author: Stavros Baloyannis
Publsiher: BoD – Books on Demand
Total Pages: 124
Release: 2020-03-11
ISBN: 1789855314
Category: Medical
Language: EN, FR, DE, ES & NL

Mitochondria and Brain Disorders Book Excerpt:

The mitochondrion is a unique and ubiquitous organelle that contains its own genome, encoding essential proteins that are major components of the respiratory chain and energy production system. Mitochondria play a dominant role in the life and function of eukaryotic cells including neurons and glia, as their survival and activity depend upon mitochondrial energy production and supply. Besides energy production, mitochondria also play a vital role in calcium homeostasis and may induce apoptosis by excitotoxicity. Mitochondrial dysfunction is related to common neurological diseases, such as Parkinson's disease, Alzheimer's disease, Friedreich's ataxia, Huntington's disease, and Multiple Sclerosis. An efficient treatment of mitochondrial dysfunction would open new horizons in the therapeutic perspectives of a substantial number of inflammatory and degenerative neurological disorders.

Mitochondria in Neurological Disorders

Mitochondria in Neurological Disorders
Author: Rajat Sandhir
Publsiher: Academic Press
Total Pages: 500
Release: 2022-06-15
ISBN: 9780128217313
Category: Medical
Language: EN, FR, DE, ES & NL

Mitochondria in Neurological Disorders Book Excerpt:

Mitochondria in Neurological Diseases highlights various therapeutic approaches targeting mitochondria in neurological conditions. Focused on diverse neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, depression, and Amyotrophic lateral sclerosis, topics span basic mitochondrial physiology to mitochondrial dynamics and to the altered states of the nervous system. This book is appropriate for anyone interested in learning more about the physiological and pathophysiological functions of mitochondria in the nervous system. Provides up-to-date information on role of mitochondria in nervous system for graduate students and researchers Presents chapters on energy substrate utilization, calcium handling, mitochondria-organelle communication, and cell signaling Discusses recent techniques in understanding mitochondrial functions in the nervous system Emphasizes the role of altered mitochondrial functions in various neurological conditions and their potential treatment strategies for targeting mitochondria Includes chapter references (key articles, books, protocols) for additional detailed study

The Functions Disease Related Dysfunctions and Therapeutic Targeting of Neuronal Mitochondria

The Functions  Disease Related Dysfunctions  and Therapeutic Targeting of Neuronal Mitochondria
Author: J. Marie Hardwick
Publsiher: John Wiley & Sons
Total Pages: 448
Release: 2015-11-09
ISBN: 1118709233
Category: Medical
Language: EN, FR, DE, ES & NL

The Functions Disease Related Dysfunctions and Therapeutic Targeting of Neuronal Mitochondria Book Excerpt:

This book focuses on dysfunctional neuronal mitochondria, their functions, cell pathways, and properties and how they relate to therapeutics and pharmacology. For scientists and researchers in both industry and academia, this book provides detailed discussion, examples, and approaches, to illustrate the potential of mitochondria as therapeutic targets for neuronal diseases. The book is divided into three parts that cover mitochondrial structure and function, mitochondrial dysfunction and its relationship to neuronal disease, and targeting of dysfunctional neuronal mitochondria for drug development and therapeutics. 30 chapters cover hot and emerging topics in the field, like mitophagy and mitochondria in Parkinson's disease, bioenergetics, genetic diseases, the link between mitochondrial metabolic syndrome and Alzheimer's disease, Huntington's disease, novel neuroprotective agents, mitochondria-targeted peptide antioxidants, molecular chaperones for improved sensor recovery, mitochondrial function in diabetic neuropathy, among others. This book encompasses all of the necessary tools and perspectives to help decipher challenges in the field and lead to the development of strategies in more targeted approaches and personalized treatments.

Mitochondrial Dysfunction in Neurodegenerative Disorders

Mitochondrial Dysfunction in Neurodegenerative Disorders
Author: Amy Katherine Reeve,Kim Jennifer Krishnan,Michael R. Duchen,Doug M Turnbull
Publsiher: Springer Science & Business Media
Total Pages: 242
Release: 2011-11-15
ISBN: 9780857297013
Category: Medical
Language: EN, FR, DE, ES & NL

Mitochondrial Dysfunction in Neurodegenerative Disorders Book Excerpt:

As age related diseases increase in prevalence and impact more significantly on medical resources it is imperative to understand these diseases and the mechanisms behind their progression. New research has stimulated a growing interest in mitochondrial involvement in neurodegenerative disorders such as Parkinson’s disease, Alzheimer’s disease and multiple sclerosis and the mechanisms which lead from mitochondrial dysfunction to neurodegeneration. Mitochondrial Dysfunction in Neurodegenerative Disorders brings together contributions from leaders in the field internationally on the various ways in which mitochondrial dysfunction contributes to the pathogenesis of these diseases, guiding the reader through the basic functions of mitochondria and the mechanisms that lead to their dysfunction, to the consequences of this dysfunction on neuronal function before finishing with the modelling of these disorders and discussion of new potential therapeutic targets. Mitochondrial Dysfunction in Neurodegenerative Disorders provides an accessible, authoritative guide to this important area for neurologists; research and clinical neuroscientists; neuropathologists; and residents with an interest in clinical research.

Mitochondrial Dynamics and Neurodegeneration

Mitochondrial Dynamics and Neurodegeneration
Author: Bingwei Lu
Publsiher: Springer Science & Business Media
Total Pages: 260
Release: 2011-05-16
ISBN: 940071291X
Category: Medical
Language: EN, FR, DE, ES & NL

Mitochondrial Dynamics and Neurodegeneration Book Excerpt:

Mitochondria are essential organelles in eukaryotic cells that control such diverse processes as energy metabolism, calcium buffering, and cell death. Recent studies have revealed that changes in mitochondrial morphology by fission and fusion, a process known as mitochondrial dynamics, is particularly important for neuronal function and survival. Defects in this process are commonly found in neurodegenerative diseases, offering a new paradigm for investigating mechanisms of neurodegeneration. To provide researchers working on neurodegenerative diseases and mitochondria with updated information on this rapidly progressing field, we have invited experts in the field to critically review recent progresses and identify future research directions. The topics include genetics of mitochondrial dynamics, mitochondrial dynamics and bioenergetics, autophagy, apoptosis, and axonal transport, and its role in neurological diseases, including Alzheimer’s, Parkinson’s, and Huntington’s diseases.

Pharmacology of Mitochondria

Pharmacology of Mitochondria
Author: Harpreet Singh,Shey-Shing Sheu
Publsiher: Springer
Total Pages: 493
Release: 2017-08-11
ISBN: 3319573136
Category: Medical
Language: EN, FR, DE, ES & NL

Pharmacology of Mitochondria Book Excerpt:

This special book is conceived to highlight mitochondrial structural and functional integrity and how they are associated with several human diseases such as cardiovascular, cancer, renal, neurological disorder, and genetic disorders. The chapters contributed by leading mitochondrial researchers in the handbook will take us through the novel pharmacological strategies via mitochondria to understand their physiological and pathological role as well as present them as therapeutic targets.

Role of Mitochondria in Neurological Disease

Role of Mitochondria in Neurological Disease
Author: Anthony S. Basile
Publsiher: Unknown
Total Pages: 118
Release: 2002
ISBN: 1928374650XXX
Category: Electronic Book
Language: EN, FR, DE, ES & NL

Role of Mitochondria in Neurological Disease Book Excerpt:

Mitochondria dependent Local Caspase Activation and Mitofusin 2 mediated Mitophagy in Neurodegeneration

Mitochondria dependent Local Caspase Activation and Mitofusin 2 mediated Mitophagy in Neurodegeneration
Author: Hao Chen
Publsiher: Unknown
Total Pages: 135
Release: 2020
ISBN: 1928374650XXX
Category: Bone remodeling
Language: EN, FR, DE, ES & NL

Mitochondria dependent Local Caspase Activation and Mitofusin 2 mediated Mitophagy in Neurodegeneration Book Excerpt:

Mitochondria are critical regulators of neuronal physiology. They play a pivotal role in energy supply and Ca2+ buffering. Thus, mitochondria can sustain the synapse and neuronal function. In this regard, the mitochondria with an impaired capacity of bioenergetics or Ca2+ buffering will lead to synapse failure and neurodegeneration. Moreover, emerging evidence has shown that damaged mitochondria are also involved in local caspase activation, which coincides with spine pruning and neurodegeneration. However, the impacts of local caspase signaling on spine dynamics and neurodegeneration are still not clarified. To clarify them is critical for neurological disorders, in which the mitochondrial deficits are prominent and hard to be fixed. Additionally, as a pivotal mitochondrial enzyme – the F1Fo ATP synthase, dysfunction of it will lead to diseases with spinopathy. To this end, we inhibited the F1Fo ATP synthase by applying the sublethal oligomycin A to primary cultured neurons. Then, it induced the mitochondrial dysfunction and local caspase signaling. Following this, we blocked the caspase signaling through its inhibitor to determine whether it can rescue the spine elimination. In this case, we can dissect the caspase signaling out of mitochondrial energy supply and examine how much the caspase signaling attributes to spine pruning. Furthermore, we will find new ways to prevent the senescence of neurons through caspase inhibition. Moreover, mitochondrial quality control is of paramount importance for neuronal survival. Notably, mitophagy is a vital mechanism for maintenance of mitochondrial quality control. A previous study has shown that Mitofusin2 (Mfn2) plays a key role in mediating mitophagy in cardiomyocytes, which was demonstrated by decreased mitophagy in Mfn2 knockdown cardiomyocytes. In addition, lowered expression levels of Mfn2 have been repeatedly found in many neurodegenerative diseases like Alzheimer’s disease, which is characterized by the accumulation of damaged mitochondrial and mitophagosomes in neurons. In this regard, reduced Mfn2 expression may lead to compromised mitophagy and mitochondrial quality control. However, whether Mfn2 is indispensable for facilitating mitophagy has not been fully investigated. To this end, we knocked down Mfn2 in primary cultured neurons. Then, we examined the state of mitophagy. Intriguingly, we observed more mitophagosomes formation in Mfn2 knock-down neurons. It indicates the Mfn2 is not necessary for mitophagy induction. Such discrepancy may arise from the heterogeneity of different cell types. Also, it may arise from some alternative adaptor proteins, which can activate mitophagy. From previous reports, people pulled down the conjugated proteins from the outer mitochondrial membrane (OMM) of senescent and healthy neurons. After screening them by mass spectrum, they found that several OMM proteins may be the potential receptors for mitophagosome formation. Among them, Voltage-Dependent Anion Channel (VDAC) is the one most reported for mitophagy induction. Accordingly, we will further knockdown VDAC in Mfn2 knock-down neurons and examine the mitophagy states. In this case, we can determine whether VDAC can work as an Mfn2-independent alternative trigger for mitophagy in neurons. In all, both local caspases signaling and mitophagy play essential roles in neurodegeneration. Regulation of them may provide us new avenues for treating neurodegenerative diseases..

Mitochondrial Dynamics and Neurodegeneration

Mitochondrial Dynamics and Neurodegeneration
Author: Bingwei Lu
Publsiher: Springer
Total Pages: 260
Release: 2013-01-02
ISBN: 9789400712928
Category: Medical
Language: EN, FR, DE, ES & NL

Mitochondrial Dynamics and Neurodegeneration Book Excerpt:

Mitochondria are essential organelles in eukaryotic cells that control such diverse processes as energy metabolism, calcium buffering, and cell death. Recent studies have revealed that changes in mitochondrial morphology by fission and fusion, a process known as mitochondrial dynamics, is particularly important for neuronal function and survival. Defects in this process are commonly found in neurodegenerative diseases, offering a new paradigm for investigating mechanisms of neurodegeneration. To provide researchers working on neurodegenerative diseases and mitochondria with updated information on this rapidly progressing field, we have invited experts in the field to critically review recent progresses and identify future research directions. The topics include genetics of mitochondrial dynamics, mitochondrial dynamics and bioenergetics, autophagy, apoptosis, and axonal transport, and its role in neurological diseases, including Alzheimer’s, Parkinson’s, and Huntington’s diseases.

Mitochondria and the Future of Medicine

Mitochondria and the Future of Medicine
Author: Lee Know
Publsiher: Chelsea Green Publishing
Total Pages: 272
Release: 2018-02-19
ISBN: 1603587683
Category: Medical
Language: EN, FR, DE, ES & NL

Mitochondria and the Future of Medicine Book Excerpt:

With information for patients and practitioners on optimizing mitochondrial function for greater health and longevity Why do we age? Why does cancer develop? What's the connection between heart failure and Alzheimer's disease, or infertility and hearing loss? Can we extend lifespan, and if so, how? What is the Exercise Paradox? Why do antioxidant supplements sometimes do more harm than good? Many will be amazed to learn that all these questions, and many more, can be answered by a single point of discussion: mitochondria and bioenergetics. In Mitochondria and the Future of Medicine, Naturopathic Doctor Lee Know tells the epic story of mitochondria, the widely misunderstood and often-overlooked powerhouses of our cells. The legendary saga began over two billion years ago, when one bacterium entered another without being digested, which would evolve to create the first mitochondrion. Since then, for life to exist beyond single-celled bacteria, it's the mitochondria that have been responsible for this life-giving energy. By understanding how our mitochondria work, in fact, it is possible to add years to our lives, and life to our years. Current research, however, has revealed a dark side: many seemingly disconnected degenerative diseases have tangled roots in dysfunctional mitochondria. However, modern research has also endowed us with the knowledge on how to optimize its function, which is of critical importance to our health and longevity. Lee Know offers cutting-edge information on supplementation and lifestyle changes for mitochondrial optimization, such as CoQ10, D-Ribose, cannabinoids, and ketogenic dietary therapy, and how to implement their use successfully. Mitochondria and the Future of Medicine is an invaluable resource for practitioners interested in mitochondrial medicine and the true roots of chronic illness and disease, as well as anyone interested in optimizing their health.

Interactions Between the Ubiquitin Proteasome System and Mitochondria in Ageing and Neurological Disorders

Interactions Between the Ubiquitin Proteasome System and Mitochondria in Ageing and Neurological Disorders
Author: Anonim
Publsiher: Unknown
Total Pages: 316
Release: 2015
ISBN: 1928374650XXX
Category: Electronic Book
Language: EN, FR, DE, ES & NL

Interactions Between the Ubiquitin Proteasome System and Mitochondria in Ageing and Neurological Disorders Book Excerpt:

Molecular Basis of Neurological Disorders and Their Treatment

Molecular Basis of Neurological Disorders and Their Treatment
Author: J.W. Gorrod,A. Albano,E. Ferrari,S. Papa
Publsiher: Springer Science & Business Media
Total Pages: 337
Release: 2012-12-06
ISBN: 9401131147
Category: Medical
Language: EN, FR, DE, ES & NL

Molecular Basis of Neurological Disorders and Their Treatment Book Excerpt:

cytochemical techniques (ICC) which provide a useful adjunct to investigations by immunoblotting. A particular advantage of a cytochemical approach to the investiga tion of mitochondrial disorders is that it allows the mosaic distribution of certain of these defects to be detected, whereas the tissue homogeniza tion involved in conventional enzyme assays or immunoblotting precludes this. A further advantage of MEA or ICC is that only small amounts of tissue are needed, which is important since many of the affected patients are infants or small children. The main aim of this communica tion is to outline ways in which these techniques can be used in the diagnosis and further investigation of mitochondrial disorders. Reference will be made not only to those situations in which MEA and ICC offer advantages over standard enzyme asays and immunoblotting but also to contexts in which the reverse applies. 4. 2 MATERIALS AND METHODS Muscle biopsies for cytochemical investigation were snap-frozen using isopentane cooled to - 150°C in liquid nitrogen. Samples were stored in heat-sealed polythene packets in the vapour phase of liquid nitrogen containers. 4. 2. 1 Microphotometric enzyme assays Frozen sections 8 Jlm thick were cut using a Reichert-J ung Frigocut cryostat microtome equipped with motor-driven cutting action to maintain maximal reproducibility of section thickness. Sections were picked up on microscope slides and air-dried for 15 min at room temperature.

Mitochondrial Disorders in Neurology

Mitochondrial Disorders in Neurology
Author: Anthony H.V. Schapira,S. Dimauro
Publsiher: Butterworth-Heinemann
Total Pages: 264
Release: 2013-10-22
ISBN: 1483193691
Category: Health & Fitness
Language: EN, FR, DE, ES & NL

Mitochondrial Disorders in Neurology Book Excerpt:

Mitochondrial Disorders in Neurology provides an overview of mitochondrial diseases. This book discusses the effects of mitochondrial dysfunction based on the relevant biochemistry and molecular genetics. The abnormal muscle and mitochondrial morphology in a variety of clinical presentations from isolated ophthalmoplegia to severe encephalopathy are also elaborated. This text likewise deliberates Leber's hereditary optic neuropathy, neurodegenerative disorders, and respiratory chain defects. Other topics covered include mitochondrial DNA and the genetics of mitochondrial disease; cytochrome oxidase deficiency; use of tissue culture in the diagnosis of mitochondrial disease; and advances in mitochondrial genetics. This publication is a good source for clinicians and students concerned with the defective mitochondrial function.

Mitochondrial Myopathies

Mitochondrial Myopathies
Author: Anonim
Publsiher: Unknown
Total Pages: 135
Release: 2007
ISBN: 1928374650XXX
Category: Electronic Book
Language: EN, FR, DE, ES & NL

Mitochondrial Myopathies Book Excerpt:

Mitochondria

Mitochondria
Author: Anonim
Publsiher: Elsevier
Total Pages: 519
Release: 2001-05-23
ISBN: 008052253X
Category: Science
Language: EN, FR, DE, ES & NL

Mitochondria Book Excerpt:

This title employs biochemical, cell biological, and genetic approaches to study mitochondrial structure, function, and biogenesis. Also of interest are the consequences of impaired mitochondrial function on cells, tissues, and organs. The book is full of step-by-step "how to" methods with sample results, interpretations, and pitfalls. There is a unique set of appendices that include gene catalogs, mtDNA maps, and reagents for probing respiratory chain function. Finally, there are applications of state-of-the art microarray and gene chip technologies. Isolation of mitochondria from commonly used cells and tissues Assays for mitochondrial activities, including respiration, ATP production, permeability, protein import, and interactions with the cytoskeleton Biochemical and optical methods for studying protein-protein interactions in mitochondria Approaches to studying mitochondrial replication, transcription, and translation Transmitochondrial technologies Methods in microassay data analysis

Metabolic Syndrome and Neurological Disorders

Metabolic Syndrome and Neurological Disorders
Author: Akhlaq A. Farooqui,Tahira Farooqui
Publsiher: John Wiley & Sons
Total Pages: 576
Release: 2013-09-26
ISBN: 111839528X
Category: Medical
Language: EN, FR, DE, ES & NL

Metabolic Syndrome and Neurological Disorders Book Excerpt:

Metabolic Syndrome and Neurological Disorders brings together information on the cluster of common pathologies which cause metabolic syndrome - abdominal obesity linked to an excess of visceral fat, insulin resistance, dyslipidemia and hypertension - to provide a comprehensive and cutting edge exploration of the link between metabolic syndrome and neurological disorders. Metabolic syndrome is recognized to play a role in neurological disorders such as stroke, Alzheimer's disease, and depression. For the first time in book form, Metabolic Syndrome and Neurological Disorders covers the molecular mechanisms thought to underlie this mirror relationship, as well as how lifestyle and other factors such as oxidative stress and inflammation may play a role in the disease. Grounded in a series of epidemiological studies of metabolic-cognitive syndrome, this book will be a valuable reference for researchers, dietitians, nutritionists, and physicians.

Frontiers in Clinical Drug Research CNS and Neurological Disorders Volume 10

Frontiers in Clinical Drug Research   CNS and Neurological Disorders  Volume 10
Author: Atta-ur-Rahman,Zareen Amtul
Publsiher: Bentham Science Publishers
Total Pages: 360
Release: 2022-04-07
ISBN: 9815040685
Category: Science
Language: EN, FR, DE, ES & NL

Frontiers in Clinical Drug Research CNS and Neurological Disorders Volume 10 Book Excerpt:

Frontiers in Clinical Drug Research - CNS and Neurological Disorders is a book series that brings updated reviews to readers interested in advances in the development of pharmaceutical agents for the treatment of central nervous system (CNS) and other nerve disorders. The scope of the book series covers a range of topics including the medicinal chemistry, pharmacology, molecular biology and biochemistry of contemporary molecular targets involved in neurological and CNS disorders. Reviews presented in the series are mainly focused on clinical and therapeutic aspects of novel drugs intended for these targets. Frontiers in Clinical Drug Research - CNS and Neurological Disorders is a valuable resource for pharmaceutical scientists and postgraduate students seeking updated and critical information for developing clinical trials and devising research plans in the field of neurology. Volume 10 of the series continues to present novel information about new and interesting approaches to treat common neurological disorders, with a focus on neurodegeneration and pain medicine. The volume presents 7 detailed reviews in total. - Neurodegenerative disease: prevention and treatment through plant extracts therapy - Emerging novel approaches and recent advances in Parkinson’s disease treatment and diagnosis - Neurotrophic factors to combat neurodegeneration - Neural bases of executive function in ADHD children as assessed using FNIRS - Modulation of mesenchymal stem cells, glial cells and the immune system by oligodeoxynucleotides as a novel multi-target therapeutic approach against chronic pain - Chronic pain: focus on anticonvulsants - A review of the impact of testosterone on brain and aging-related decline in brain behavioural function

Tau Pathology in Neurological Disorders

Tau Pathology in Neurological Disorders
Author: Sonia Do Carmo,A. Claudio Cuello,Maria Grazia Spillantini
Publsiher: Frontiers Media SA
Total Pages: 135
Release: 2021-11-12
ISBN: 2889716252
Category: Science
Language: EN, FR, DE, ES & NL

Tau Pathology in Neurological Disorders Book Excerpt:

Mitochondrial Metabolism

Mitochondrial Metabolism
Author: Jalal Pourahmad,Mohsen Rezaei
Publsiher: Elsevier
Total Pages: 316
Release: 2021-08-12
ISBN: 0128224169
Category: Science
Language: EN, FR, DE, ES & NL

Mitochondrial Metabolism Book Excerpt:

Mitochondrial Metabolism: An Approach for Disease Management covers mitotherapy from three combined perspectives, Pharmacology, Toxicology and Biochemistry. After an introduction from world-renowned experts, the book's chapters cover the balancing role in reduction/oxidation mitochondria play, mitochondria as targets for therapeutics through its metabolism, mitochondrial contributions to the cell death process, mitochondrial response to environmental toxicants, the mitochondrial role in aging, the impact of calorie restrictive diets, new advances in the identification of altered mitochondria associated signaling pathways in carcinogenesis, and much more. This book provides bioscientists new horizons to realize the importance of mitochondria in present-day research on therapies dealing with mitochondria associated chronic diseases, including diabetes, cancer and neurodegenerative disorders. Details the significant role of mitochondria in chronic diseases Presents new insights on the targeting of mitochondria for therapeutic purposes Includes updated results on mitotherapy and other mitochondria-oriented therapies

The Impact of Ferritins in the Nigrostriatal System

The Impact of Ferritins in the Nigrostriatal System
Author: Amanda Marie Snyder
Publsiher: Unknown
Total Pages: 236
Release: 2009
ISBN: 1928374650XXX
Category: Electronic Book
Language: EN, FR, DE, ES & NL

The Impact of Ferritins in the Nigrostriatal System Book Excerpt:

Iron status is higher in the substantia nigra than in other brain regions but can fluctuate as function of diet, genetics, and disease. Because iron can influence neuronal cell death and dopamine function, the body tightly controls the supply of iron needed for tasks such as a cofactor for enzymes but also has mechanisms in place to sequester iron to limit oxidative stress. The major protein that accomplishes this latter task is ferritin, with the ferroxidase properties belonging to the H subunit. In this thesis, mice genetically altered to be heterozygous for a mutation in the H-ferritin gene were utilized to examine the impact of H-ferritin-deficiency on the dopaminergic nigrostriatal system. The distribution of mitochondrial ferritin, a protein structurally and functionally similar to Hferritin, was also explored in mouse and human brain. Using high-resolution magic angle spin proton magnetic resonance spectroscopy (HR-MAS 1H MRS), significant increases in glutamate levels were found in the striatum and ventral midbrain in H-ferritin-deficient animals as compared to wild-type. While lactate was increased in the ventral midbrain of H-ferritin-deficient animals, it was decreased in the striatum. Dopamine transporter (DAT) expression in the substantia nigra and striatum was unchanged with age or by the loss of ferritin. Overall, the neurochemical profile is suggestive of neuronal iron deficiency. Because iron deficiency causes long-term effects on the dopaminergic system and may influence the onset of or susceptibility to neurologic disorders, the number of tyrosine hydroxylase dopaminergic neurons in the substantia nigra pars compacta was evaluated using stereology. The results indicate that there is no loss in dopaminergic cell number with age or genotype. However, when mice are challenged with neurotoxic insult by the pesticides paraquat (1, 1'-dimethyl-4,4'-bipyridinium) and maneb (manganese ethylenebisdithiocarbamate), two agents that are effective in inducing selective and irreversible loss of tyrosine hydroxylase-positive neurons in the substantia nigra that is akin to what is seen in Parkinson's disease, there is significant cell loss in the 12 month old H-ferritin-deficient mice compared to control. A surprising finding was that H-ferritin was not detectable in the substantia nigra pars compacta at 4, 8, or 12 months of age regardless of genotype or toxin exposure. The lack of detectable H-ferritin in the substantia nigra opened the possibility that another ferritin, such as mitochondrial ferritin (FtMt), could be an anti-oxidant protein in the brain. FtMt has ferroxidase activity and is similar to H-ferritin except for its cellular localization to the mitochondria. Mitochondrial dysfunction has been linked to Parkinson's disease, which further makes mitochondrial ferritin a protein of interest. We found FtMt expression in almost all regions of the brain, although staining intensity varies between regions. Both neurons and oligodendrocytes prominently immunostain for mitochondrial ferritin. Mice deficient in H-ferritin do not differ in the mitochondrial ferritin staining pattern or intensity as compared to C57/BL6 mice, which further supports existing data suggesting that these two proteins are distinct. Given the importance and relationship between iron and mitochondrial activity, understanding the role of mitochondrial ferritin in neurologic disorders may be important. We explored the expression of FtMt in Restless legs syndrome (RLS), a disorder that involves decreased iron availability in the brain. FtMt levels in human autopsy samples from the putamen and substantia nigra revealed that the RLS nigra had significantly more FtMt than controls; there was not a significant difference in FtMt in the putamen. Immunohistochemical analysis indicated that neuromelanin-containing neurons were the predominant cell type expressing FtMt, and staining intensity in the neurons from the RLS samples was consistently greater than that seen in controls. In addition, cytochrome c oxidase staining, reflective of the number of mitochondria, followed a similar staining pattern to FtMt. The increased number of mitochondria in neurons in RLS coupled with increased FtMt could contribute to insufficient cytosolic iron levels in RLS neurons and the symptoms of this disorder. Overall, the data presented in this thesis suggest that alterations in ferritin levels, despite relatively low levels of expression of both H-ferritin and mitochondrial ferritin, have a wide-ranging impact on cellular energetics and metabolism. The H-ferritindeficient mice are a model in which the study of iron mismanagement can be used to study neurological disorders such as Parkinson's disease and may be a model for RLS.