The Role of Mitochondrial Genes in Neurodegenerative Disorders

: Mitochondrial disorders are clinically heterogeneous, resulting from nuclear gene and mitochondrial mutations that disturb the mitochondrial functions and dynamics. There is a lack of evidence linking mtDNA mutations to neurodegenerative disorders, mainly due to the absence of noticeable neuropathological lesions in postmortem samples. This review describes various gene mutations in Alzheimer's disease, Parkinson's disease, Amyotrophic Lateral Sclerosis, Multiple Sclerosis, and Stroke. These abnormalities, including PINK1, Parkin, and SOD1 mutations, seem to reveal mitochondrial dysfunctions due to either mtDNA mutation or deletion, the mechanism of which remains unclear in depth.

Download Full-text

Alternation of Mitochondrial and Golgi Apparatus in Neurodegenerative Disorders

Advances in Medical Diagnosis, Treatment, and Care - Handbook of Research on Critical Examinations of Neurodegenerative Disorders ◽

10.4018/978-1-5225-5282-6.ch005 ◽

2019 ◽

pp. 102-128

Author(s):

Sonia Sharma ◽

Paramjeet Kaur ◽

Shallina Gupta ◽

Sushant Sharma

Keyword(s):

Golgi Apparatus ◽

Neurodegenerative Disorders ◽

Morphological Changes ◽

Mitochondrial Dysfunctions ◽

Over Expression ◽

Associated Proteins ◽

Environmental Causes ◽

Altered Proteins ◽

Lateral Sclerosis ◽

Apoptotic Factors

Neurodegenerative disorders (NDs) are characterized by dysfunction and loss of neurons associated with altered proteins that accumulate in the human brain and peripheral organs. Mitochondrial and Golgi apparatus (GA) dysfunctions are supposed to be responsible for various NDs. Damaged mitochondria do not produce sufficient adenosine triphosphate (ATP) and produce reactive oxygen species (ROS) and pro-apoptotic factors. Mitochondrial dysfunctions may be caused by various factors such as environmental causes, mutations in both nuclear or mitochondrial deoxyribonucleic acid (DNA), that code many mitochondrial components. Three factors that are mainly responsible for the morphological changes in GA are certain pathological conditions, drugs, and over expression of Golgi associated proteins. In this chapter, common aspects of mitochondrial and GA dysfunction concerned about NDs are summarized and described for Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD).

Download Full-text

Mitochondrial Dysfunctions: A Red Thread across Neurodegenerative Diseases

International Journal of Molecular Sciences ◽

10.3390/ijms21103719 ◽

2020 ◽

Vol 21 (10) ◽

pp. 3719 ◽

Cited By ~ 10

Author(s):

Serena Stanga ◽

Anna Caretto ◽

Marina Boido ◽

Alessandro Vercelli

Keyword(s):

Neurodegenerative Diseases ◽

Neuronal Degeneration ◽

Muscular Atrophy ◽

Early Event ◽

Mitochondrial Dysfunctions ◽

The Core ◽

Optimal Functioning ◽

Mitochondrial Functions ◽

Lateral Sclerosis ◽

Common Target

Mitochondria play a central role in a plethora of processes related to the maintenance of cellular homeostasis and genomic integrity. They contribute to preserving the optimal functioning of cells and protecting them from potential DNA damage which could result in mutations and disease. However, perturbations of the system due to senescence or environmental factors induce alterations of the physiological balance and lead to the impairment of mitochondrial functions. After the description of the crucial roles of mitochondria for cell survival and activity, the core of this review focuses on the “mitochondrial switch” which occurs at the onset of neuronal degeneration. We dissect the pathways related to mitochondrial dysfunctions which are shared among the most frequent or disabling neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and Huntington’s, Amyotrophic Lateral Sclerosis, and Spinal Muscular Atrophy. Can mitochondrial dysfunctions (affecting their morphology and activities) represent the early event eliciting the shift towards pathological neurobiological processes? Can mitochondria represent a common target against neurodegeneration? We also review here the drugs that target mitochondria in neurodegenerative diseases.

Download Full-text

Tau Accumulation via Reduced BAG3-mediated Autophagy Is Required for GGGGCC Repeat Expansion-Induced Neurodegeneration

10.1101/727008 ◽

2019 ◽

Author(s):

Xue Wen ◽

Ping An ◽

Hexuan Li ◽

Zijian Zhou ◽

Yimin Sun ◽

...

Keyword(s):

Tau Protein ◽

Neurodegenerative Disorders ◽

Motor Performance ◽

Molecular Mechanisms ◽

Repeat Expansion ◽

Cag Repeats ◽

Reduced Activity ◽

Lateral Sclerosis

SUMMARYExpansions of trinucleotide or hexanucleotide repeats lead to several neurodegenerative disorders including Huntington disease (HD, caused by the expanded CAG repeats (CAGr) in the HTT gene) and amyotrophic lateral sclerosis (ALS, could be caused by the expanded GGGGCC repeats (G4C2r) in the C9ORF72 gene), of which the molecular mechanisms remain unclear. Here we demonstrate that loss of the Drosophila orthologue of tau protein (dtau) significantly rescued in vivo neurodegeneration, motor performance impairments, and shortened life-span in Drosophila models expressing mutant HTT protein with expanded CAGr or the expanded G4C2r. Importantly, expression of human tau (htau4R) restored the disease-relevant phenotypes that were mitigated by the loss of dtau, suggesting a conserved role of tau in neurodegeneration. We further discovered that G4C2r expression increased dtau accumulation, possibly due to reduced activity of BAG3-mediated autophagy. Our study reveals a conserved role of tau in G4C2r-induced neurotoxicity in Drosophila models, providing mechanistic insights and potential therapeutic targets.

Download Full-text

Mitochondria and Neurodegeneration

Bioscience Reports ◽

10.1007/s10540-007-9038-z ◽

2007 ◽

Vol 27 (1-3) ◽

pp. 87-104 ◽

Cited By ~ 82

Author(s):

Lucia Petrozzi ◽

Giulia Ricci ◽

Noemi J. Giglioli ◽

Gabriele Siciliano ◽

Michelangelo Mancuso

Keyword(s):

Alzheimer’S Disease ◽

Amyotrophic Lateral Sclerosis ◽

Neurodegenerative Diseases ◽

Mitochondrial Dysfunction ◽

Huntington's Disease ◽

Neurodegenerative Disorders ◽

Molecular Abnormalities ◽

Lateral Sclerosis ◽

Lines Of Evidence

Many lines of evidence suggest that mitochondria have a central role in ageing-related neurodegenerative diseases. However, despite the evidence of morphological, biochemical and molecular abnormalities in mitochondria in various tissues of patients with neurodegenerative disorders, the question “is mitochondrial dysfunction a necessary step in neurodegeneration?” is still unanswered. In this review, we highlight some of the major neurodegenerative disorders (Alzheimer's disease, Parkinson's disease, Amyotrophic lateral sclerosis and Huntington's disease) and discuss the role of the mitochondria in the pathogenetic cascade leading to neurodegeneration.

Download Full-text

Maldistribution of Neurofilaments, Disease Pathogenesis, and Amyotrophic Lateral Sclerosis

US Neurology ◽

10.17925/usn.2010.05.02.30 ◽

2010 ◽

Vol 05 (02) ◽

pp. 30

Author(s):

Rodolphe Perrot ◽

Jean-Pierre Julien ◽

◽

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Mouse Models ◽

Intermediate Filaments ◽

Neurodegenerative Disorders ◽

Disease Pathogenesis ◽

Lateral Sclerosis

Accumulations of neuronal intermediate filaments (IFs) are a characteristic of many human neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS). However, IF formation and the contribution of IF aggregates to the pathogenesis of ALS remain unclear. Here, we review the possible mechanisms underlying the formation of IF accumulations and the mouse models that have been used to investigate the role of IF proteins in ALS pathogenesis.

Download Full-text

Role of Prostaglandins in Multiple Sclerosis

Current Pharmaceutical Design ◽

10.2174/1381612826666200107141328 ◽

2020 ◽

Vol 26 (7) ◽

pp. 730-742

Author(s):

Surendra Gulla ◽

Dakshayani Lomada ◽

Anusha Lade ◽

Reddanna Pallu ◽

Madhava C. Reddy

Keyword(s):

Multiple Sclerosis ◽

Central Nervous System ◽

Nervous System ◽

Neurodegenerative Disorders ◽

Cognitive Disability ◽

Demyelinating Disorder ◽

Mediators Of Inflammation ◽

The Central Nervous System ◽

Lateral Sclerosis

: Multiple sclerosis (MS) is an autoimmune demyelinating disorder with chronic inflammation in the central nervous system, manifested by both physical and cognitive disability. Neuroinflammation and neurodegeneration are the phenomena that appear in the central nervous system associated with various neurodegenerative disorders, including MS, Alzheimer’s diseases, amyotrophic lateral sclerosis and Parkinson’s disease. Prostaglandins are one of the major mediators of inflammation that exhibit an important function in enhancing neuroinflammatory and neurodegenerative processes. These mediators would help understand the pathophysiology of MS as the combination of antagonists or agonists of prostaglandins receptors could be beneficial during the treatment of MS. The present review focuses on the role played by different prostaglandins and the enzymes which produced them in the etiopathogenesis of MS.

Download Full-text

Metals and neurodegeneration

Oxford Textbook of Neurologic and Neuropsychiatric Epidemiology ◽

10.1093/med/9780198749493.003.0040 ◽

2020 ◽

pp. 417-424

Author(s):

Susan Peters ◽

Anne E Visser ◽

Marc Weisskopf ◽

Marianthi-Anna Kioumourtzoglou ◽

Roel Vermeulen

Keyword(s):

Neurodegenerative Disorders ◽

Epidemiological Studies ◽

Metal Exposure ◽

Reverse Causality ◽

Long Latency ◽

Contaminated Food ◽

Genetic And Environmental Factors ◽

Occupational Settings ◽

Lateral Sclerosis

Neurodegenerative disorders, including Alzheimer’s disease, amyotrophic lateral sclerosis, and Parkinson’s disease, are thought to be caused by both genetic and environmental factors. Several metals and metalloids have been identified as neurotoxicants and exposure may occur, for example, via air pollution, contaminated food or drinking water, cigarette smoke, or in occupational settings. Epidemiological evidence of associations between metal exposure and neurodegenerative disorders, however, is scarce. Here we provide an overview of metals that have been suggested to play a role in neurodegeneration. Investigating these associations is challenged by accurate case ascertainment due to complicated diagnosis, multifactorial disease mechanisms, long latency requiring retrospective exposure assessment, and possible reverse causality when comparing cases and controls. Further research on understanding the role of metals in the pathology of neurodegenerative disorders is needed. Future epidemiological studies should be large and high-quality studies to provide the crucial evidence on metal exposures as possible risk factors.

Download Full-text

Mitochondrial Dysfunction and Chronic Inflammation in Polycystic Ovary Syndrome

International Journal of Molecular Sciences ◽

10.3390/ijms22083923 ◽

2021 ◽

Vol 22 (8) ◽

pp. 3923

Author(s):

Siarhei A. Dabravolski ◽

Nikita G. Nikiforov ◽

Ali H. Eid ◽

Ludmila V. Nedosugova ◽

Antonina V. Starodubova ◽

...

Keyword(s):

Chronic Inflammation ◽

Polycystic Ovary ◽

Low Grade ◽

Causative Role ◽

Mitochondrial Dysfunctions ◽

Mtdna Mutations ◽

Targeted Treatments ◽

Tnf Α ◽

Novel Biomarkers

Polycystic ovarian syndrome (PCOS) is the most common endocrine–metabolic disorder affecting a vast population worldwide; it is linked with anovulation, mitochondrial dysfunctions and hormonal disbalance. Mutations in mtDNA have been identified in PCOS patients and likely play an important role in PCOS aetiology and pathogenesis; however, their causative role in PCOS development requires further investigation. As a low-grade chronic inflammation disease, PCOS patients have permanently elevated levels of inflammatory markers (TNF-α, CRP, IL-6, IL-8, IL-18). In this review, we summarise recent data regarding the role of mtDNA mutations and mitochondrial malfunctions in PCOS pathogenesis. Furthermore, we discuss recent papers dedicated to the identification of novel biomarkers for early PCOS diagnosis. Finally, traditional and new mitochondria-targeted treatments are discussed. This review intends to emphasise the key role of oxidative stress and chronic inflammation in PCOS pathogenesis; however, the exact molecular mechanism is mostly unknown and requires further investigation.

Download Full-text

Role of neuro-sonography of peripheral nerves as a diagnostic and a differentiation tool of amyotrophic lateral sclerosis

The Egyptian Journal of Neurology Psychiatry and Neurosurgery ◽

10.1186/s41983-021-00389-y ◽

2021 ◽

Vol 57 (1) ◽

Author(s):

Rana Zakaria Ahmed Mohamed ◽

Haitham Hamdy Salem ◽

Hossam Moussa El-Sayed Sakr ◽

Hossam-Eldin Mahmoud Afifi ◽

Ahmed Mohammed Elsadek ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Differential Diagnosis ◽

Early Diagnosis ◽

Motor Neuron ◽

Motor Neuron Disease ◽

Neurodegenerative Disorders ◽

Peripheral Nerves ◽

Radiological Criteria ◽

Lateral Sclerosis

Abstract Background Motor neuron disease is a heterogeneous group of progressive neurodegenerative disorders, most common of which is amyotrophic lateral sclerosis (ALS). There are many clinical and radiological criteria to diagnose amyotrophic lateral sclerosis and to differentiate it from other motor neuron disease and neurodegenerative disorders. Neuro-sonography is one of the easily applied tools to diagnose and differentiate ALS. ALS diagnosis is delayed up to 3 years according to some authors due to the wide differential diagnosis, with cervical degeneration being a common misdiagnosis. The objective of this study was to evaluate the role of neuro-sonography in diagnosis and differentiation of amyotrophic lateral sclerosis from other causes of progressive mixed upper and lower motor neuron lesion. Results A total neuro-sonography score at a cut-off point (≤ 127) predicted patients with ALS, with good (85%) accuracy, sensitivity = 73% and specificity = 83% (p < 0.01) and Lt median arm score at a cut-off point (≤ 6) predicted patients with ALS, with good (88%) accuracy, sensitivity = 86% and specificity = 86% (p < 0.01) and the median nerve at the arm level was the most sensitive and specific nerve to predict patients with ALS. Conclusion Neuro-sonography of peripheral nerves is a recent, noninvasive, accessible technique that can be used in early diagnosis of ALS.

Download Full-text