α-Synuclein Promotes Mitochondrial Deficit and Oxidative Stress
Leigh J. Hsu,Yutaka Sagara,Armando Arroyo,Edward Rockenstein,Abbyann Sisk,Margaret Mallory,Jeffrey J. Wong,Takato Takenouchi,Makoto Hashimoto,Eliezer Masliah +9 more
TLDR
Results suggest that abnormal accumulation of α-synuclein could lead to mitochondrial alterations that may result in oxidative stress and, eventually, cell death.Abstract:
Abnormal accumulation of the presynaptic protein α-synuclein has recently been implicated in the pathogenesis of Alzheimer’s and Parkinson’s diseases. Because neurodegeneration in these conditions might be associated with mitochondrial dysfunction and oxidative stress, the effects of α-synuclein were investigated in a hypothalamic neuronal cell line (GT1-7). α-Synuclein overexpression in these cells resulted in formation of α-synuclein-immunopositive inclusion-like structures and mitochondrial alterations accompanied by increased levels of free radicals and decreased secretion of gonadotropin-releasing hormone. These alterations were ameliorated by pretreatment with anti-oxidants such as vitamin E. Taken together these results suggest that abnormal accumulation of α-synuclein could lead to mitochondrial alterations that may result in oxidative stress and, eventually, cell death.read more
Citations
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A Mitochondrial Paradigm of Metabolic and Degenerative Diseases, Aging, and Cancer: A Dawn for Evolutionary Medicine
TL;DR: The mitochondria provide a direct link between the authors' environment and their genes and the mtDNA variants that permitted their forbears to energetically adapt to their ancestral homes are influencing their health today.
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Autophagy in human health and disease.
TL;DR: This review discusses the cellular process of autophagy (“self-eating”), which plays key roles in normal development of the immune system and adaptation to stress, as well as in a wide range of disease states.
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Oxidative stress in neurodegeneration: cause or consequence?
TL;DR: A review of the evidence for oxidative stress in neurodegeneration and how this relates to other cellular events can be found in this article, where a growing number of in vitro and in vivo models that emulate human disease pathology is aiding scientists in deciphering just where oxidative stress intersects with other cellular processes.
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Unfolding the role of protein misfolding in neurodegenerative diseases.
TL;DR: The aim of this article is to review the literature on the molecular mechanism of protein misfolding and aggregation, its role in Neurodegeneration and the potential targets for therapeutic intervention in neurodegenerative diseases.
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Alpha-synuclein and neurodegenerative diseases
TL;DR: The molecular properties of the synucleins, the different diseases characterized by the accumulation of α-synuclein, and the possible mechanisms by which dysfunction ofα- synuclein might lead to neurodegeneration are reviewed.
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