Immunosenescence as a modifiable driver of neurodegenerative diseases: Pathways and multidimensional emerging strategies for Alzheimer's and Parkinson's diseases.
- 1Central Laboratory, the Affiliated Hospital of Yanbian University(Yanbian Hospital), Yanji, 133000, PR China; Key Laboratory of Pathobiology, Yanbian University, Yanji, 133000, PR China.
- 2Department of Neurology, Jilin City Central Hospital, Jilin, 132001, PR China. Electronic address: [email protected].
- 3Central Laboratory, the Affiliated Hospital of Yanbian University(Yanbian Hospital), Yanji, 133000, PR China; Key Laboratory of Pathobiology, Yanbian University, Yanji, 133000, PR China. Electronic address: [email protected].
Abstract
Immunosenescence represents a core upstream driver of Alzheimer's disease (AD) and Parkinson's disease (PD), exerting its pathological effects through four mechanistically interconnected cascades: chronic inflammatory imbalance mediated by the senescence-associated secretory phenotype (SASP), oxidative stress arising from immune-metabolic reprogramming, protein homeostasis dysfunction caused by autophagy-lysosomal failure, and disrupted neuro-immune crosstalk secondary to breakdown of central nervous system (CNS) immune privilege. Current clinical practice remains largely constrained to neurotransmitter-based symptomatic management, which can neither arrest upstream pathological progression nor restore lost neuronal populations. Emerging intervention strategies targeting immunosenescence, including senolytic agents, antioxidant and metabolic modulators, autophagy restoration, and precision-targeted nanocarrier delivery, have demonstrated substantial capacity to delay disease progression in preclinical and early clinical investigations. These strategies act through selective clearance of senescent immune cells, remodeling of the neuroinflammatory microenvironment, and restoration of cellular quality-control mechanisms. The multidimensional treatment strategy approaches from the perspectives of artificial intelligence (AI) guided target discovery, nanocarrier engineering, and gut microbiota intervention to simultaneously address multiple nodes in the immunosenescence network, thereby overcoming the inherent limitations of single-target strategies. This review consolidates current mechanistic evidence and translational data to establish immunosenescence as an actionable therapeutic target and to provide a conceptual framework for precision disease-modifying therapy in AD and PD.
Related
- CO018 | THE MOLI-SANI RISK SCORE, A MEASURE OF MODIFIABLE CARDIOVASCULAR RISK, PREDICTS NON-CARDIOVASCULAR MORTALITY AND SELECTED CANCERS, BUT NOT NEURODEGENERATIVE DISEASES
- Modeling Strategies for Neurodegenerative Diseases: In Vitro, In Vivo and In Silico Frameworks
- Sex differences in genetic liability to modifiable Alzheimer's disease risk factors
- Neurodegenerative Diseases: Epidemiology, Risk Factors, Classification, Pathophysiology, Clinical Features, Diagnosis, and Therapeutic Strategies.
- Emerging Therapeutic Strategies for Neurodegenerative Diseases: A Comprehensive Review of Recent Advances and Future Directions
BibTeX
@article{zhao2026immunosenescence,
title = {{Immunosenescence as a modifiable driver of neurodegenerative diseases: Pathways and multidimensional emerging strategies for Alzheimer's and Parkinson's diseases.}},
author = {Jingyu Zhao and Linzhuo Qu and Hongjian Guan and Huiying Che and Fei Shi and Yang Yang},
journal = {Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics},
year = {2026},
month = oct,
doi = {10.1016/j.neurot.2026.e01096},
url = {https://europepmc.org/article/MED/42863347},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Immunosenescence as a modifiable driver of neurodegenerative diseases: Pathways and multidimensional emerging strategies for Alzheimer's and Parkinson's diseases.
AU - Jingyu Zhao
AU - Linzhuo Qu
AU - Hongjian Guan
AU - Huiying Che
AU - Fei Shi
AU - Yang Yang
PY - 2026
DA - 2026/10/12
JO - Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics
DO - 10.1016/j.neurot.2026.e01096
UR - https://europepmc.org/article/MED/42863347
AB - Immunosenescence represents a core upstream driver of Alzheimer's disease (AD) and Parkinson's disease (PD), exerting its pathological effects through four mechanistically interconnected cascades: chronic inflammatory imbalance mediated by the senescence-associated secretory phenotype (SASP), oxidative stress arising from immune-metabolic reprogramming, protein homeostasis dysfunction caused by autophagy-lysosomal failure, and disrupted neuro-immune crosstalk secondary to breakdown of central nervous system (CNS) immune privilege. Current clinical practice remains largely constrained to neurotransmitter-based symptomatic management, which can neither arrest upstream pathological progression nor restore lost neuronal populations. Emerging intervention strategies targeting immunosenescence, including senolytic agents, antioxidant and metabolic modulators, autophagy restoration, and precision-targeted nanocarrier delivery, have demonstrated substantial capacity to delay disease progression in preclinical and early clinical investigations. These strategies act through selective clearance of senescent immune cells, remodeling of the neuroinflammatory microenvironment, and restoration of cellular quality-control mechanisms. The multidimensional treatment strategy approaches from the perspectives of artificial intelligence (AI) guided target discovery, nanocarrier engineering, and gut microbiota intervention to simultaneously address multiple nodes in the immunosenescence network, thereby overcoming the inherent limitations of single-target strategies. This review consolidates current mechanistic evidence and translational data to establish immunosenescence as an actionable therapeutic target and to provide a conceptual framework for precision disease-modifying therapy in AD and PD.
SN - 1933-7213
SN - 1878-7479
ER -