Metabolic energy decline coupled dysregulation of catecholamine metabolism in physiologically highly active neurons: implications for selective neuronal death in Parkinson's disease

Loading...
Thumbnail Image
Issue Date
2024
Embargo End Date
Authors
Wimalasena, Kandatege
Adetuyi, Oluwatosin
Eldani, Maya
Advisor
Citation

Wimalasena, K., Adetuyi, O., Eldani, M. Metabolic energy decline coupled dysregulation of catecholamine metabolism in physiologically highly active neurons: implications for selective neuronal death in Parkinson's disease. (2024). Frontiers in Aging Neuroscience, 16, art. no. 1339295. DOI: 10.3389/fnagi.2024.1339295

Abstract

Parkinson's disease (PD) is an age-related irreversible neurodegenerative disease which is characterized as a progressively worsening involuntary movement disorder caused by the loss of dopaminergic (DA) neurons in substantia nigra pars compacta (SNpc). Two main pathophysiological features of PD are the accumulation of inclusion bodies in the affected neurons and the predominant loss of neuromelanin-containing DA neurons in substantia nigra pars compacta (SNpc) and noradrenergic (NE) neurons in locus coeruleus (LC). The inclusion bodies contain misfolded and aggregated ?-synuclein (?-Syn) fibrils known as Lewy bodies. The etiology and pathogenic mechanisms of PD are complex, multi-dimensional and associated with a combination of environmental, genetic, and other age-related factors. Although individual factors associated with the pathogenic mechanisms of PD have been widely investigated, an integration of the findings to a unified causative mechanism has not been envisioned. Here we propose an integrated mechanism for the degeneration of DA neurons in SNpc and NE neurons in LC in PD, based on their unique high metabolic activity coupled elevated energy demand, using currently available experimental data. The proposed hypothetical mechanism is primarily based on the unique high metabolic activity coupled elevated energy demand of these neurons. We reason that the high vulnerability of a selective group of DA neurons in SNpc and NE neurons in LC in PD could be due to the cellular energy modulations. Such cellular energy modulations could induce dysregulation of DA and NE metabolism and perturbation of the redox active metal homeostasis (especially copper and iron) in these neurons. Copyright © 2024 Wimalasena, Adetuyi and Eldani.

Table of Content
Description
© 2024 Wimalasena, Adetuyi and Eldani. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
publication.page.dc.relation.uri