An Update on the Critical Role of α-Synuclein in Parkinson’s Disease and Other Synucleinopathies: from Tissue to Cellular and Molecular Levels

Iris N. Serratos, Elizabeth Hernández-Pérez, Carolina Campos, Michael Aschner, Abel Santamaría

Research output: Contribution to journalReview articlepeer-review

Abstract

The aggregation of alpha-synuclein (α-Syn) plays a critical role in the development of Parkinson’s disease (PD) and other synucleinopathies. α-Syn, which is encoded by the SNCA gene, is a lysine-rich soluble amphipathic protein normally expressed in neurons. Located in the cytosolic domain, this protein has the ability to remodel itself in plasma membranes, where it assumes an alpha-helix conformation. However, the protein can also adopt another conformation rich in cross-beta sheets, undergoing mutations and post-translational modifications, then leading the protein to an unusual aggregation in the form of Lewy bodies (LB), which are cytoplasmic inclusions constituted predominantly by α-Syn. Pathogenic mechanisms affecting the structural and functional stability of α-Syn — such as endoplasmic reticulum stress, Golgi complex fragmentation, disfunctional protein degradation systems, aberrant interactions with mitochondrial membranes and nuclear DNA, altered cytoskeleton dynamics, disrupted neuronal plasmatic membrane, dysfunctional vesicular transport, and formation of extracellular toxic aggregates — contribute all to the pathogenic progression of PD and synucleinopathies. In this review, we describe the collective knowledge on this topic and provide an update on the critical role of α-Syn aggregates, both at the cellular and molecular levels, in the deregulation of organelles affecting the cellular homeostasis and leading to neuronal cell death in PD and other synucleinopathies.

Original languageEnglish (US)
JournalMolecular Neurobiology
DOIs
StateAccepted/In press - 2021

Keywords

  • Lewy bodies
  • Membrane biological interactions
  • Organelles
  • Parkinson’s disease
  • Post-translational modifications
  • Synucleinopathies
  • α-Synuclein

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

Fingerprint

Dive into the research topics of 'An Update on the Critical Role of α-Synuclein in Parkinson’s Disease and Other Synucleinopathies: from Tissue to Cellular and Molecular Levels'. Together they form a unique fingerprint.

Cite this