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Disturbed Mitochondrial Dynamics And Neurodegenerative Disorders Pdf

disturbed mitochondrial dynamics and neurodegenerative disorders pdf

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Metrics details. Under the microscope, neuronal accumulation of abnormal tau proteins and amyloid plaques are two pathological hallmarks in affected brain regions.

Huntington disease HD is an inherited neurodegenerative disease resulting from an abnormal expansion of polyglutamine in huntingtin Htt. Compromised oxidative stress defense systems have emerged as a contributing factor to the pathogenesis of HD. Indeed activation of the Nrf2 pathway, which plays a prominent role in mediating antioxidant responses, has been considered as a therapeutic strategy for the treatment of HD. Given the fact that there is an interrelationship between impairments in mitochondrial dynamics and increased oxidative stress, in this present study we examined the effect of mutant Htt mHtt on these two parameters.

Abnormalities of Mitochondrial Dynamics in Neurodegenerative Diseases

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Mitochondria do not exist as isolated organelles; instead, they form a highly interconnected tubular network throughout the cell.

The state of this dynamic mitochondrial network under both physiological and disease conditions is dictated by the balance between mitochondrial pro-fusion and pro-fission forces. Mounting evidence implicates disturbed mitochondrial dynamics in the pathogenesis of complex neurodegenerative disorders such as Alzheimer disease, Parkinson disease and Huntington disease. Although treatment options for disorders of mitochondrial dynamics are currently limited, the future looks promising for the development of novel neuroprotective strategies and innovative gene therapy approaches.

Mitochondria form a highly interconnected tubular network throughout the cell via a dynamic process, with mitochondrial segments fusing and breaking apart continuously. Strong evidence has emerged to implicate disturbed mitochondrial fusion and fission as central pathological components underpinning a number of childhood and adult-onset neurodegenerative disorders. Several proteins that regulate the morphology of the mitochondrial network have been identified, the most widely studied of which are optic atrophy 1 and mitofusin 2.

Pathogenic mutations that disrupt these two pro-fusion proteins cause autosomal dominant optic atrophy and axonal Charcot—Marie—Tooth disease type 2A, respectively.

These disorders predominantly affect specialized neurons that require precise shuttling of mitochondria over long axonal distances. Considerable insight has also been gained by carefully dissecting the deleterious consequences of imbalances in mitochondrial fusion and fission on respiratory chain function, mitochondrial quality control mitophagy , and programmed cell death. Interestingly, these cellular processes are also implicated in more-common complex neurodegenerative disorders, such as Alzheimer disease and Parkinson disease, indicating a common pathological thread and a close relationship with mitochondrial structure, function and localization.

Understanding how these fundamental processes become disrupted will prove crucial to the development of therapies for the growing number of neurodegenerative disorders linked to disturbed mitochondrial dynamics. Chan, D. Mitochondria: dynamic organelles in disease, aging, and development. Cell , — Yu-Wai-Man, P. Inherited mitochondrial optic neuropathies.

Reilly, M. Saporta, A. Charcot—Marie—Tooth disease subtypes and genetic testing strategies. Wong, L. Google Scholar. Belenguer, P. Acta , — Chen, H. Mitofusins Mfn1 and Mfn2 coordinately regulate mitochondrial fusion and are essential for embryonic development.

Cell Biol. Eura, Y. Two mitofusin proteins, mammalian homologues of FZO, with distinct functions are both required for mitochondrial fusion. Lenaers, G. OPA1 functions in mitochondria and dysfunctions in optic nerve. Frezza, C. OPA1 controls apoptotic cristae remodeling independently from mitochondrial fusion.

Amati-Bonneau, P. OPA1 RH mutation in optic atrophy associated with sensorineural deafness. Zanna, C. OPA1 mutations associated with dominant optic atrophy impair oxidative phosphorylation and mitochondrial fusion. Brain , — Loson, O. Cell 24 , — Otera, H.

Mff is an essential factor for mitochondrial recruitment of Drp1 during mitochondrial fission in mammalian cells. Rostovtseva, T. Bax activates endophilin B1 oligomerization and lipid membrane vesiculation. Tondera, D. The mitochondrial protein MTP18 contributes to mitochondrial fission in mammalian cells. Cell Sci. Takahashi, Y. Cell Death Differ. Olichon, A.

The human dynamin-related protein OPA1 is anchored to the mitochondrial inner membrane facing the inter-membrane space.

FEBS Lett. OPA1 alternate splicing uncouples an evolutionary conserved function in mitochondrial fusion from a vertebrate restricted function in apoptosis. Duvezin-Caubet, S. OPA1 processing reconstituted in yeast depends on the subunit composition of the m-AAA protease in mitochondria. Cell 18 , — Martinelli, P.

Emerging roles of mitochondrial proteases in neurodegeneration. Acta , 1—10 Ishihara, N. Regulation of mitochondrial morphology through proteolytic cleavage of OPA1. EMBO J.

Griparic, L. Regulation of the mitochondrial dynamin-like protein Opa1 by proteolytic cleavage. Song, Z. McQuibban, G. Mitochondrial membrane remodelling regulated by a conserved rhomboid protease. Nature , — Cipolat, S. Ehses, S. Head, B. Mishra, P. Proteolytic cleavage of Opa1 stimulates mitochondrial inner membrane fusion and couples fusion to oxidative phosphorylation.

Cell Metab. Pich, S. Agier, V. Defective mitochondrial fusion, altered respiratory function, and distorted cristae structure in skin fibroblasts with heterozygous OPA1 mutations. Chevrollier, A. Hereditary optic neuropathies share a common mitochondrial coupling defect. Cogliati, S. Mitochondrial cristae shape determines respiratory chain supercomplexes assembly and respiratory efficiency.

Lodi, R. Defective mitochondrial adenosine triphosphate production in skeletal muscle from patients with dominant optic atrophy due to OPA1 mutations. OPA1 mutations impair mitochondrial function in both pure and complicated dominant optic atrophy. Brain , e Del Bo, R. Mutated mitofusin 2 presents with intrafamilial variability and brain mitochondrial dysfunction. Neurology 71 , — Area-Gomez, E. Upregulated function of mitochondria-associated ER membranes in Alzheimer disease.

An intimate liaison: spatial organization of the endoplasmic reticulum-mitochondria relationship. Kornmann, B. An ER—mitochondria tethering complex revealed by a synthetic biology screen. Science , — Merkwirth, C.

Mitochondrial Dysfunction: a Potential Therapeutic Target to Treat Alzheimer’s Disease

The system can't perform the operation now. Try again later. Citations per year. Duplicate citations. The following articles are merged in Scholar. Their combined citations are counted only for the first article. Merged citations.

Mitochondrial Dysfunctions in Neurodegenerative Diseases: Relevance to Alzheimer’s Disease

Mitochondria dysfunction in the pathogenesis of Alzheimer’s disease: recent advances

Several shreds of evidence have indicated that the mitochondrial function is severely compromised under AD pathogenesis. Most of the recent therapeutic strategies have been conversed to treat AD by pinpointing the pathways involved in the pathophysiology of AD. In AD, mitochondria progressively lose their proper functions that are ultimately responsible for their accumulation and removal via the autophagic process, which is called mitophagy that further worsens the progression of this incapacitating disease. The present review is intended to discuss the recent advancements in the frontiers of mitochondrial dysfunction and consequent therapeutic strategies that have been employed to treat AD. This is a preview of subscription content, access via your institution. Rent this article via DeepDyve. J Alzheimers Dis 20 2 —

Thank you for visiting nature. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser or turn off compatibility mode in Internet Explorer. In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. Mitochondria do not exist as isolated organelles; instead, they form a highly interconnected tubular network throughout the cell. The state of this dynamic mitochondrial network under both physiological and disease conditions is dictated by the balance between mitochondrial pro-fusion and pro-fission forces.


PDF | Neurodegenerative diseases are a group of heterogeneous diseases characterized by the gradual, progressive and selective reduction.


Fei Gao, Jianmin Zhang; Mitochondrial quality control and neurodegenerative diseases. Neuronal Signal 21 December ; 2 4 : NS Mitochondria homeostasis is sustained by the mitochondrial quality control MQC system, which is crucial for cellular health, especially in the maintenance of functional mitochondria.

Neurodegenerative diseases are incurable and devastating neurological disorders characterized by the progressive loss of the structure and function of neurons in the central nervous system or peripheral nervous system. Mitochondria, organelles found in most eukaryotic cells, are essential for neuronal survival and are involved in a number of neuronal functions. Mitochondria are highly dynamic organelles that undergo continuous fusion, fission, and transport, the processes of which not only control mitochondrial morphology and number but also regulate mitochondrial function and location. In this review, after a brief discussion of molecular mechanisms regulating mitochondrial fusion, fission, distribution, and trafficking, as well as the important role of mitochondrial dynamics for neuronal function, we review previous and the most recent studies about mitochondrial dynamic abnormalities observed in various major neurodegenerative diseases and discuss the possibility of targeting mitochondrial dynamics as a likely novel therapeutic strategy for neurodegenerative diseases. Due to their limited glycolytic capacity and extremely metabolically active nature, neurons in the brain are energetically demanding cells requiring the delicate maintenance of mitochondrial function [ 5 ].

A growing body of evidence suggests that defects in mitochondrial metabolism and particularly of electron transport chain may play a role in pathogenesis of AD.

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Intracellular and Intercellular Mitochondrial Dynamics in Parkinson’s Disease

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4 Comments

  1. Sydney F.

    05.06.2021 at 11:49
    Reply

    However, the dysfunction of mitochondria has long been recognized as a key component in the progression of the disease.

  2. Ernest L.

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  4. Vick B.

    11.06.2021 at 23:10
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    Interestingly, these cellular processes are also implicated in more-common complex neurodegenerative disorders, such as Alzheimer disease.

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