Epigenetic Mechanisms in Neurodegenerative Diseases: From Genetic Regulation to Therapeutic Potential
4 affiliations
- 1College of Pharmaceutical Science, Dali University, Dali 671003, China
- 2College of Chinese Materia Medica, Yunnan University of Chinese Medicine, Kunming 650500, China
- 3Key Laboratory of Traditional Chinese Medicine for Prevention and Treatment of Neuropsychiatric Diseases, Yunnan University of Chinese Medicine, Kunming 650500, China
- 4The First Clinical Medical College, Yunnan University of Chinese Medicine, Kunming 650500, China
Abstract
Neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS), are multifactorial disorders in which genetic susceptibility alone cannot account for sporadic onset, clinical diversity, or age-dependent progression. Epigenetic mechanisms—DNA methylation, histone modifications, non-coding RNAs, and m6A RNA methylation—bridge environmental and intracellular cues to stable gene expression changes. Emerging evidence associates epigenetic dysregulation with amyloid-β/tau pathology in AD, α-synuclein pathology in PD, and TDP-43/C9orf72-associated toxicity in ALS, while functional studies suggest that selected epigenetic alterations may contribute to these processes. In this narrative review, we distinguish associative, functional, and mechanistic evidence using claim-specific criteria based on experimental perturbation, direct molecular assessment, and pathway-dependence or rescue testing, while considering the study system. We further evaluate the translational promise of epigenetic biomarkers in liquid biopsies, while emphasizing the major barriers that separate bench findings from bedside application, including poor target specificity, limited blood–brain barrier penetration, and the absence of biomarker-guided patient stratification. By integrating pathological mechanisms, biomarker development, and therapeutic strategies, this review argues that future epigenetic research in neurodegeneration must prioritize causal validation, CNS-penetrant drug development, and prospective trials integrating epigenetic profiling to achieve meaningful clinical impact.
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BibTeX
@article{lv2026epigenetic,
title = {{Epigenetic Mechanisms in Neurodegenerative Diseases: From Genetic Regulation to Therapeutic Potential}},
author = {Xiaoman Lv and Mincong Huang and Wenjuan Long and Xinyao Li and Zhongyang Hu and Yujun Feng and Jiarong Du and Qiongrong Long and Yanxin Chen and Mingqin Shi and Dongdong Qin},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27209322},
url = {https://www.mdpi.com/1422-0067/27/20/9322},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Epigenetic Mechanisms in Neurodegenerative Diseases: From Genetic Regulation to Therapeutic Potential
AU - Xiaoman Lv
AU - Mincong Huang
AU - Wenjuan Long
AU - Xinyao Li
AU - Zhongyang Hu
AU - Yujun Feng
AU - Jiarong Du
AU - Qiongrong Long
AU - Yanxin Chen
AU - Mingqin Shi
AU - Dongdong Qin
PY - 2026
DA - 2026/10/20
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27209322
UR - https://www.mdpi.com/1422-0067/27/20/9322
AB - Neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS), are multifactorial disorders in which genetic susceptibility alone cannot account for sporadic onset, clinical diversity, or age-dependent progression. Epigenetic mechanisms—DNA methylation, histone modifications, non-coding RNAs, and m6A RNA methylation—bridge environmental and intracellular cues to stable gene expression changes. Emerging evidence associates epigenetic dysregulation with amyloid-β/tau pathology in AD, α-synuclein pathology in PD, and TDP-43/C9orf72-associated toxicity in ALS, while functional studies suggest that selected epigenetic alterations may contribute to these processes. In this narrative review, we distinguish associative, functional, and mechanistic evidence using claim-specific criteria based on experimental perturbation, direct molecular assessment, and pathway-dependence or rescue testing, while considering the study system. We further evaluate the translational promise of epigenetic biomarkers in liquid biopsies, while emphasizing the major barriers that separate bench findings from bedside application, including poor target specificity, limited blood–brain barrier penetration, and the absence of biomarker-guided patient stratification. By integrating pathological mechanisms, biomarker development, and therapeutic strategies, this review argues that future epigenetic research in neurodegeneration must prioritize causal validation, CNS-penetrant drug development, and prospective trials integrating epigenetic profiling to achieve meaningful clinical impact.
SN - 1422-0067
ER -