Age-related increase in caveolin-1 expression facilitates cell-to-cell transmission of α-synuclein in neurons

Mol Brain. 2021 Jul 28;14(1):122. doi: 10.1186/s13041-021-00834-2.

Abstract

Parkinson's disease (PD) is the second most prevalent neurodegenerative disease, with aging being considered the greatest risk factor for developing PD. Caveolin-1 (Cav-1) is known to participate in the aging process. Recent evidence indicates that prion-like propagation of misfolded α-synuclein (α-syn) released from neurons to neighboring neurons plays an important role in PD progression. In the present study, we demonstrated that cav-1 expression in the brain increased with age, and considerably increased in the brain of A53T α-syn transgenic mice. Cav-1 overexpression facilitated the uptake of α-syn into neurons and formation of additional Lewy body-like inclusion bodies, phosphorylation of cav-1 at tyrosine 14 was found to be crucial for this process. This study demonstrates the relationship between age and α-syn spread and will facilitate our understanding of the molecular mechanism of the cell-to-cell transmission of α-syn.

Keywords: Aging; Caveolin-1; Cell-to-cell transmission; Endocytosis; Parkinson’s disease; α-synuclein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / metabolism*
  • Animals
  • Brain / pathology
  • Caveolin 1 / metabolism*
  • Cell Line, Tumor
  • Cells, Cultured
  • Endocytosis
  • Humans
  • Inclusion Bodies / metabolism
  • Lewy Bodies / metabolism
  • Male
  • Membrane Microdomains
  • Mice
  • Mice, Inbred C57BL
  • Models, Biological
  • Neurons / metabolism*
  • Phosphorylation
  • Phosphotyrosine / metabolism
  • Proteolysis
  • Rats
  • Rats, Sprague-Dawley
  • alpha-Synuclein / metabolism*

Substances

  • Caveolin 1
  • alpha-Synuclein
  • Phosphotyrosine