NAD+ signaling in Parkinson's disease: molecular mechanisms and therapeutic perspectives
- 1Tianbao Hospital , ,
- 2Xinjiang Medical University , ,
- 3The Affiliated Hospital to Changchun University of Chinese Medicine , ,
Abstract
Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder worldwide, characterized by the progressive loss of dopaminergic neurons in the substantia nigra, accumulation of α-synuclein (α-syn), mitochondrial dysfunction, and neuroinflammation. Nicotinamide adenine dinucleotide (NAD ⁺ ), a crucial coenzyme involved in cellular energy metabolism, DNA repair, and epigenetic regulation, declines with aging and is markedly reduced in the brains of patients with PD. Emerging evidence suggests that supplementation with NAD ⁺ precursors, including nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), exerts neuroprotective effects through multiple mechanisms, such as activation of the mitochondrial unfolded protein response (UPR∧mt), enhancement of autophagy, and suppression of excessive poly(ADP-ribose) polymerase 1 (PARP1) activation. This review summarizes the central role of NAD ⁺ dysregulation in the pathogenesis of PD, with particular emphasis on the interplay between NAD ⁺ depletion, mitochondrial quality control, proteostasis, and neuroinflammation. Furthermore, we discuss recent advances in NAD ⁺ -boosting strategies in PD models and clinical studies, highlighting their potential therapeutic implications for PD intervention.
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BibTeX
@article{wang2026signaling,
title = {{NAD+ signaling in Parkinson's disease: molecular mechanisms and therapeutic perspectives}},
author = {Tianbao Wang and Xue Zhou and Xinhua Chen},
journal = {Frontiers in neurology},
year = {2026},
month = sep,
doi = {10.3389/fneur.2026.1943801},
url = {https://europepmc.org/article/PMC/PMC13663023},
note = {CC BY},
}
RIS
TY - JOUR
TI - NAD+ signaling in Parkinson's disease: molecular mechanisms and therapeutic perspectives
AU - Tianbao Wang
AU - Xue Zhou
AU - Xinhua Chen
PY - 2026
DA - 2026/09/30
JO - Frontiers in neurology
DO - 10.3389/fneur.2026.1943801
UR - https://europepmc.org/article/PMC/PMC13663023
AB - Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder worldwide, characterized by the progressive loss of dopaminergic neurons in the substantia nigra, accumulation of α-synuclein (α-syn), mitochondrial dysfunction, and neuroinflammation. Nicotinamide adenine dinucleotide (NAD ⁺ ), a crucial coenzyme involved in cellular energy metabolism, DNA repair, and epigenetic regulation, declines with aging and is markedly reduced in the brains of patients with PD. Emerging evidence suggests that supplementation with NAD ⁺ precursors, including nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), exerts neuroprotective effects through multiple mechanisms, such as activation of the mitochondrial unfolded protein response (UPR∧mt), enhancement of autophagy, and suppression of excessive poly(ADP-ribose) polymerase 1 (PARP1) activation. This review summarizes the central role of NAD ⁺ dysregulation in the pathogenesis of PD, with particular emphasis on the interplay between NAD ⁺ depletion, mitochondrial quality control, proteostasis, and neuroinflammation. Furthermore, we discuss recent advances in NAD ⁺ -boosting strategies in PD models and clinical studies, highlighting their potential therapeutic implications for PD intervention.
SN - 1664-2295
ER -