α-Synuclein is a pathological link and therapeutic target for Parkinson's disease and traumatic brain injury

Med Hypotheses. 2013 Oct;81(4):675-80. doi: 10.1016/j.mehy.2013.07.025. Epub 2013 Aug 6.

Abstract

Parkinson's disease (PD) affects more than 1% of population over 65 and it is characterized by gradual loss of nigrostriatal dopaminergic neurons and wide spread accumulation of α-synuclein. Collectively 30% of familial and 3-5% of sporadic form of PD are associated with genetic mutation. Compelling evidence implicates that in addition to inherited factors, acquired co-morbidities contribute to PD pathology. Here, we hypothesize that traumatic brain injury (TBI) exacerbates nigrostriatal dopaminergic degeneration by modulating PD-associated genes including α-synuclein, DJ-1, LRRK2, among others. Thus this article will present speculative arguments of a genetic component contributing to this TBI and PD pathological overlap.

MeSH terms

  • Brain Injuries / metabolism
  • Brain Injuries / physiopathology*
  • Dopaminergic Neurons / metabolism
  • Dopaminergic Neurons / pathology*
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
  • Models, Biological*
  • Oncogene Proteins / metabolism
  • Parkinson Disease / metabolism
  • Parkinson Disease / physiopathology*
  • Protein Deglycase DJ-1
  • Protein Serine-Threonine Kinases / metabolism
  • alpha-Synuclein / metabolism*

Substances

  • Intracellular Signaling Peptides and Proteins
  • Oncogene Proteins
  • alpha-Synuclein
  • LRRK2 protein, human
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
  • Protein Serine-Threonine Kinases
  • PARK7 protein, human
  • Protein Deglycase DJ-1