Microglia-Mediated Neuroinflammation and Neurotrophic Factor-Induced Protection in the MPTP Mouse Model of Parkinson's Disease-Lessons from Transgenic Mice

Int J Mol Sci. 2016 Jan 26;17(2):151. doi: 10.3390/ijms17020151.

Abstract

Parkinson's disease (PD) is a neurodegenerative disease characterised by histopathological and biochemical manifestations such as loss of midbrain dopaminergic (DA) neurons and decrease in dopamine levels accompanied by a concomitant neuroinflammatory response in the affected brain regions. Over the past decades, the use of toxin-based animal models has been crucial to elucidate disease pathophysiology, and to develop therapeutic approaches aimed to alleviate its motor symptoms. Analyses of transgenic mice deficient for cytokines, chemokine as well as neurotrophic factors and their respective receptors in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD have broadened the current knowledge of neuroinflammation and neurotrophic support. Here, we provide a comprehensive review that summarises the contribution of microglia-mediated neuroinflammation in MPTP-induced neurodegeneration. Moreover, we highlight the contribution of neurotrophic factors as endogenous and/or exogenous molecules to slow the progression of midbrain dopaminergic (mDA) neurons and further discuss the potential of combined therapeutic approaches employing neuroinflammation modifying agents and neurotrophic factors.

Keywords: MPTP; Parkinson’s disease; microglia; neuroinflammation; neuroprotection; neurotrophic factors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Disease Models, Animal*
  • Humans
  • MPTP Poisoning / drug therapy
  • MPTP Poisoning / immunology*
  • MPTP Poisoning / pathology
  • Mice
  • Mice, Transgenic
  • Microglia / immunology
  • Microglia / pathology*
  • Nerve Growth Factors / metabolism*
  • Nerve Growth Factors / therapeutic use
  • Parkinson Disease / drug therapy
  • Parkinson Disease / etiology
  • Parkinson Disease / immunology*
  • Parkinson Disease / pathology
  • Receptors, Nerve Growth Factor / metabolism

Substances

  • Nerve Growth Factors
  • Receptors, Nerve Growth Factor