Logo image
Back
Selective dopaminergic neurotoxicity modulated by inherent cell-type specific neurobiology
Journal article   Peer reviewed

Selective dopaminergic neurotoxicity modulated by inherent cell-type specific neurobiology

Fatema Currim, Reeya Tanwar, Josephine M. Brown-Leung, Neha Paranjape, Jennifer Liu, Laurie H. Sanders, Jonathan A. Doorn and Jason R. Cannon
Neurotoxicology (Park Forest South), Vol.103, pp.266-287
07/02/2024
DOI: 10.1016/j.neuro.2024.06.016
PMCID: PMC11288778
PMID: 38964509
url
https://pmc.ncbi.nlm.nih.gov/articles/PMC11288778/pdf/nihms-2010413.pdfView
Open Access

Abstract

Parkinson’s disease (PD) is a debilitating neurodegenerative disease affecting millions of individuals worldwide. Hallmark features of PD pathology are the formation of Lewy bodies in neuromelanin-containing dopaminergic neurons of the substantia nigra pars compacta (SNpc), and the subsequent irreversible death of these neurons. Although genetic risk factors have been identified, around 90% of PD cases are sporadic and likely caused by environmental exposures and gene-environment interaction. Mechanistic studies have identified a variety of chemical PD risk factors. PD neuropathology occurs throughout the brain and peripheral nervous system, but it is the loss of dopamine neurons in the SNpc that produce many of the cardinal motor symptoms. Toxicology studies have found specifically the dopaminergic neuron population of the SNpc exhibit heightened sensitivity to highly variable chemical insults (both in terms of chemical structure and mechanism of neurotoxic action). Thus, it has become clear that the inherent neurobiology of nigral dopamine neurons likely underlies much of this neurotoxic response to broad insults. This review focuses on inherent neurobiology of nigral dopaminergic neurons and how such neurobiology impacts the primary mechanism of neurotoxicity. While interactions with a variety of other cell types are important in disease pathogenesis, understanding how inherent dopaminergic biology contributes to selective sensitivity and primary mechanisms of neurotoxicity is critical to advancing the field. Specifically, key biological features of dopaminergic neurons that increase neurotoxicant susceptibility. •Inherent neurobiology of nigral dopamine neurons increases toxicant vulnerability•Dopamine neurobiology and toxicant interactions are primary toxicity mechanisms•Translational Parkinson’s disease models must replicate human neurobiology
 Dopamine neurotoxicity Parkinson’s disease selectivity

Details

Metrics

12 Record Views
3 Times Cited - Web of Science
Logo image