Interactions of dopamine, iron, and alpha-synuclein linked to dopaminergic neuron vulnerability in Parkinson's disease and Neurodegeneration with Brain Iron Accumulation disorders

Autor: Rachel M. Wise, Annika Wagener, Urban M. Fietzek, Thomas Klopstock, Eugene V. Mosharov, Fabio A. Zucca, David Sulzer, Luigi Zecca, Lena F. Burbulla
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Neurobiology of Disease, Vol 175, Iss , Pp 105920- (2022)
Druh dokumentu: article
ISSN: 1095-953X
DOI: 10.1016/j.nbd.2022.105920
Popis: Dopamine metabolism, alpha-synuclein pathology, and iron homeostasis have all been implicated as potential contributors to the unique vulnerability of substantia nigra dopaminergic neurons which preferentially decline in Parkinson's disease and some rare neurodegenerative disorders with shared pathological features. However, the mechanisms contributing to disease progression and resulting in dopaminergic neuron loss in the substantia nigra are still not completely understood. Increasing evidence demonstrates that disrupted dopamine, alpha-synuclein, and/or iron pathways, when combined with the unique morphological, physiological, and metabolic features of this neuron population, may culminate in weakened resilience to multiple stressors. This review analyzes the involvement of each of these pathways in dopamine neuron physiology and function, and discusses how disrupted interplay of dopamine, alpha-synuclein, and iron pathways may synergize to promote pathology and drive the unique vulnerability to disease states. We suggest that elucidating the interactions of dopamine with iron and alpha-synuclein, and the role of dopamine metabolism in driving pathogenic phenotypes will be critical for developing therapeutics to prevent progression in diseases that show degeneration of nigral dopamine neurons such as Parkinson's disease and the rare family of disorders known as Neurodegeneration with Brain Iron Accumulation.
Databáze: Directory of Open Access Journals