Involvement of heat shock proteins and parkin/α-synuclein axis in Parkinson's disease

Mol Biol Rep. 2022 Nov;49(11):11061-11070. doi: 10.1007/s11033-022-07900-5. Epub 2022 Sep 12.

Abstract

Parkinson's disease (PD) is one of the most common neurological diseases, next only to Alzheimer's disease (AD) in terms of prevalence. It afflicts about 2-3% of individuals over 65 years old. The etiology of PD is unknown and several environmental and genetic factors are involved. From a pathological point of view, PD is characterized by the loss of dopaminergic neurons in the substantia nigra, which causes the abnormal accumulation of α-synuclein (α-syn) (a component of Lewy bodies), which subsequently interact with heat shock proteins (HSPs), leading to apoptosis. Apoptosis is a vital pathway for establishing homeostasis in body tissues, which is regulated by pro-apoptotic and anti-apoptotic factors. Recent findings have shown that HSPs, especially HSP27 and HSP70, play a pivotal role in regulating apoptosis by influencing the factors involved in the apoptosis pathway. Moreover, it has been reported that the expression of these HSPs in the nervous system is high. Apart from this finding, investigations have suggested that HSP27 and HSP70 (related to parkin) show a potent protective and anti-apoptotic impact against the damaging outcomes of mutant α-syn toxicity to nerve cells. Therefore, in this study, we aimed to investigate the relationship between these HSPs and apoptosis in patients with PD.

Keywords: Apoptosis; Heat shock proteins; Lewy bodies; Neurodegenerative disease; Parkinson’s disease; α-synuclein.

Publication types

  • Review

MeSH terms

  • Aged
  • Dopaminergic Neurons / metabolism
  • HSP27 Heat-Shock Proteins / genetics
  • HSP70 Heat-Shock Proteins / genetics
  • Heat-Shock Proteins / genetics
  • Heat-Shock Proteins / metabolism
  • Humans
  • Parkinson Disease* / genetics
  • Parkinson Disease* / metabolism
  • Ubiquitin-Protein Ligases / genetics
  • alpha-Synuclein* / genetics
  • alpha-Synuclein* / metabolism

Substances

  • alpha-Synuclein
  • HSP27 Heat-Shock Proteins
  • Heat-Shock Proteins
  • HSP70 Heat-Shock Proteins
  • Ubiquitin-Protein Ligases