Therapeutic Strategies for Immune Transformation in Parkinson's Disease

Maamoon Saleh, Milica Markovic, Katherine E. Olson, Howard E. Gendelman, R. Lee Mosley

Research output: Contribution to journalReview articlepeer-review

2 Scopus citations

Abstract

Dysregulation of innate and adaptive immunity can lead to alpha-synuclein (-syn) misfolding, aggregation, and post-translational modifications in Parkinson's disease (PD). This process is driven by neuroinflammation and oxidative stress, which can contribute to the release of neurotoxic oligomers that facilitate dopaminergic neurodegeneration. Strategies that promote vaccines and antibodies target the clearance of misfolded, modified -syn, while gene therapy approaches propose to deliver intracellular single chain nanobodies to mitigate -syn misfolding, or to deliver neurotrophic factors that support neuronal viability in an otherwise neurotoxic environment. Additionally, transformative immune responses provide potential targets for PD therapeutics. Anti-inflammatory drugs represent one strategy that principally affects innate immunity. Considerable research efforts have focused on transforming the balance of pro-inflammatory effector T cells (Teffs) to favor regulatory T cell (Treg) activity, which aims to attenuate neuroinflammation and support reparative and neurotrophic homeostasis. This approach serves to control innate microglial neurotoxic activities and may facilitate clearance of -syn aggregates accordingly. More recently, changes in the intestinal microbiome have been shown to alter the gut-immune-brain axis leading to suppressed leakage of bacterial products that can promote peripheral inflammation and -syn misfolding. Together, each of the approaches serves to interdict chronic inflammation associated with disordered immunity and neurodegeneration. Herein, we examine research strategies aimed at improving clinical outcomes in PD.

Original languageEnglish (US)
Pages (from-to)S201-S222
JournalJournal of Parkinson's Disease
Volume12
DOIs
StatePublished - Jul 18 2022

Keywords

  • -synuclein clearance
  • Immunomodulatory therapy
  • Parkinson's disease
  • adaptive immunity
  • cell-based therapies
  • gene-based therapies
  • gut-brain axis
  • innate immunity
  • neuroinflammation
  • regulatory T cells

ASJC Scopus subject areas

  • Clinical Neurology
  • Cellular and Molecular Neuroscience

Fingerprint

Dive into the research topics of 'Therapeutic Strategies for Immune Transformation in Parkinson's Disease'. Together they form a unique fingerprint.

Cite this