TY - JOUR
T1 - Therapeutic Strategies for Immune Transformation in Parkinson's Disease
AU - Saleh, Maamoon
AU - Markovic, Milica
AU - Olson, Katherine E.
AU - Gendelman, Howard E.
AU - Mosley, R. Lee
N1 - Publisher Copyright:
© 2022 - The authors.
PY - 2022/7/18
Y1 - 2022/7/18
N2 - 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.
AB - 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.
KW - -synuclein clearance
KW - Immunomodulatory therapy
KW - Parkinson's disease
KW - adaptive immunity
KW - cell-based therapies
KW - gene-based therapies
KW - gut-brain axis
KW - innate immunity
KW - neuroinflammation
KW - regulatory T cells
UR - http://www.scopus.com/inward/record.url?scp=85138881765&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85138881765&partnerID=8YFLogxK
U2 - 10.3233/JPD-223278
DO - 10.3233/JPD-223278
M3 - Review article
C2 - 35871362
AN - SCOPUS:85138881765
VL - 12
SP - S201-S222
JO - Journal of Parkinson's Disease
JF - Journal of Parkinson's Disease
SN - 1877-7171
ER -