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Generation of Alpha-Synuclein Preformed Fibrils from Monomers and Use In Vivo
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The Close Encounter Between Alpha-Synuclein and Mitochondria.

Mattia Vicario1, Domenico Cieri1, Marisa Brini2

  • 1Department of Biomedical Sciences, University of Padova, Padova, Italy.

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|June 23, 2018
PubMed
Summary
This summary is machine-generated.

Alpha-synuclein (α-syn) aggregation is key in Parkinson's disease (PD). This protein impacts mitochondrial function, suggesting a novel therapeutic target for PD by modulating α-syn within mitochondria.

Keywords:
Parkinson diseasealpha-synucleinbioenergeticsmitochondrianeurodegeneration

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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Biochemistry

Background:

  • Alpha-synuclein (α-syn) is intrinsically linked to Parkinson's disease (PD) pathogenesis.
  • Mutations and gene multiplications of α-syn cause familial PD, and it forms Lewy body aggregates.
  • Mechanisms of neuronal degeneration in PD are not fully elucidated, but mitochondrial dysfunction and impaired autophagy are implicated.

Purpose of the Study:

  • To explore the role of alpha-synuclein in controlling mitochondrial function.
  • To investigate the mechanisms by which α-syn influences mitochondrial processes in physiological and pathological conditions.
  • To survey literature on α-syn localization within mitochondria and its impact on PD.

Main Methods:

  • Literature review focusing on α-syn localization within mitochondrial sub-compartments.
  • Analysis of studies investigating α-syn's influence on mitochondrial bioenergetics, calcium handling, morphology, and ATP production.
  • Examination of the relationship between α-syn aggregation and mitochondrial function.

Main Results:

  • A fraction of cellular α-syn localizes to mitochondria under specific stimuli.
  • Alpha-synuclein directly influences key mitochondrial processes: cytochrome c release, calcium homeostasis, membrane potential, and ATP production.
  • Mitochondrial localization of α-syn may affect its aggregation state, linking it to PD pathogenesis.

Conclusions:

  • The intimate relationship between α-syn and mitochondria is crucial for understanding PD.
  • Alpha-synuclein's direct control over mitochondrial functions presents potential therapeutic targets.
  • Further research into α-syn/mitochondria interactions could reveal novel therapeutic strategies for Parkinson's disease.