Mitochondrial Dysfunction and Biogenesis in Neurodegenerative diseases: Pathogenesis and Treatment

CNS Neuroscience & Therapeutics, Journal Year: 2016, Volume and Issue: 23(1), P. 5 - 22

Published: Nov. 22, 2016

Summary Neurodegenerative diseases are a heterogeneous group of disorders that incurable and characterized by the progressive degeneration function structure central nervous system ( CNS ) for reasons not yet understood. Neurodegeneration is umbrella term death nerve cells loss brain tissue. Because their high energy requirements, neurons especially vulnerable to injury from dysfunctional mitochondria. Widespread damage mitochondria causes die because they can no longer produce enough energy. Several lines pathological physiological evidence reveal impaired mitochondrial dynamics play crucial roles in aging pathogenesis neurodegenerative diseases. As major intracellular organelles regulate both cell survival death, highly considered as potential target pharmacological‐based therapies. The purpose this review was present current status our knowledge understanding involvement dysfunction including Alzheimer's disease AD ), Parkinson's PD Huntington's HD amyotrophic lateral sclerosis ALS importance biogenesis novel therapeutic treatment. Likewise, we highlight concise overview key electron transport chain ETC. complexes well regulators regarding those

Language: Английский

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α-Synuclein Is Localized to Mitochondria-Associated ER Membranes

Journal of Neuroscience, Journal Year: 2013, Volume and Issue: 34(1), P. 249 - 259

Published: Dec. 31, 2013

Familial Parkinson disease is associated with mutations in α-synuclein (α-syn), a presynaptic protein that has been localized not only to the cytosol, but also mitochondria. We report here wild-type α-syn from cell lines, and brain tissue humans mice, present mitochondria rather mitochondria-associated endoplasmic reticulum (ER) membranes (MAM), structurally functionally distinct subdomain of ER. Remarkably, we found pathogenic point human result its reduced association MAM, coincident lower degree apposition ER mitochondria, decrease MAM function, an increase mitochondrial fragmentation compared wild-type. Although overexpression mutant α-syn-expressing cells reverted phenotype, neither fusion/MAM-tethering MFN2 nor inhibition/ablation fission DRP1 was able do so, implying operates downstream fusion/fission machinery. These novel results indicate localizes modulates morphology, these behaviors are impaired by α-syn. believe our have far-reaching implications for both understanding biology treatment synucleinopathies.

Language: Английский

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Mitostasis in Neurons: Maintaining Mitochondria in an Extended Cellular Architecture

Neuron, Journal Year: 2017, Volume and Issue: 96(3), P. 651 - 666

Published: Nov. 1, 2017

Language: Английский

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An energetic view of stress: Focus on mitochondria

Frontiers in Neuroendocrinology, Journal Year: 2018, Volume and Issue: 49, P. 72 - 85

Published: Jan. 12, 2018

Energy is required to sustain life and enable stress adaptation. At the cellular level, energy largely derived from mitochondria – unique multifunctional organelles with their own genome. Four main elements connect stress: (1) at molecular, (epi)genetic, cellular, organellar, systemic levels components of responses; (2) Glucocorticoids other steroid hormones are produced metabolized by mitochondria; (3) Reciprocally, respond neuroendocrine metabolic mediators; (4) Experimentally manipulating mitochondrial functions alters physiological behavioral responses psychological stress. Thus, endocrine that provide both signals direct Neural circuits regulating social behavior as well psychopathological processes also influenced energetics. An integrative view an energy-driven process opens new opportunities study mechanisms adaptation regulation across lifespan.

Language: Английский

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Astrocytes in Neurodegenerative Disease: Table 1.

Cold Spring Harbor Perspectives in Biology, Journal Year: 2015, Volume and Issue: 7(6), P. a020628 - a020628

Published: April 15, 2015

Hemali Phatnani and Tom Maniatis Columbia University Medical Center, Department of Biochemistry Molecular Biophysics, New York, York 10032 Correspondence: tm2472{at}columbia.edu

Language: Английский

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