Neurodegeneration: Pathways and Mechanisms

A special issue of Biology (ISSN 2079-7737). This special issue belongs to the section "Neuroscience".

Deadline for manuscript submissions: 30 November 2026 | Viewed by 4122

Special Issue Editors


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Guest Editor
Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy
Interests: oxidative stress; brain function; neurodegeneration; antioxidant capability; physical exercise
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Special Issue Information

Dear Colleagues,

Neurodegeneration denotes a complex phenomenon that primarily causes the reduction in nervous cells and the loss of their function, leading to a wide range of clinical manifestations that characterize the main neurodegenerative diseases. 

Despite the phenotypic heterogeneity of these disorders, the progressive neurodegeneration is due, in most cases, to common cellular pathways, including inflammation, increased oxidative stress, altered apoptotic mechanisms, defects in autophagy and lysosomal functions, and impaired cell metabolism, as well as to a genetic predisposition.

We are pleased to invite you to the present Special Issue, whose purpose is to investigate molecular pathways affecting neurodegeneration; original research articles and reviews are welcome. 

Research areas may include (but are not limited to) the following:

  • Oxidative stress and inflammation;
  • Apoptosis, autophagy, and lysosomal function;
  • Epigenetic mechanisms affecting neurodegeneration (exercise, diet);
  • Gut–brain

We look forward to receiving your contributions.

Dr. Ferdinando Franzoni
Dr. Giorgia Scarfò
Guest Editors

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Keywords

  • inflammation
  • oxidative stress
  • apoptosis
  • exercise
  • diet
  • cellular pathways

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Published Papers (1 paper)

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Review

31 pages, 1208 KB  
Review
Melatonin as a Guardian of Mitochondria: Mechanisms and Therapeutic Potential in Neurodegenerative Diseases
by Yanyu Bao, Guoying Miao, Nannan He, Xingting Bao, Zheng Shi, Cuilan Hu, Xiongxiong Liu, Bing Wang and Chao Sun
Biology 2026, 15(2), 189; https://doi.org/10.3390/biology15020189 - 20 Jan 2026
Cited by 2 | Viewed by 3835
Abstract
Mitochondrial dysfunction is a key early pathological process in neurodegenerative diseases (NDs), leading to oxidative stress, impaired energy metabolism, and neuronal apoptosis prior to the onset of clinical symptoms. Although mitochondria represent important therapeutic targets, effective interventions targeting mitochondrial function remain limited. This [...] Read more.
Mitochondrial dysfunction is a key early pathological process in neurodegenerative diseases (NDs), leading to oxidative stress, impaired energy metabolism, and neuronal apoptosis prior to the onset of clinical symptoms. Although mitochondria represent important therapeutic targets, effective interventions targeting mitochondrial function remain limited. This review summarizes current evidence regarding the mechanisms by which melatonin protects mitochondria and evaluates its therapeutic relevance, with a primary focus on Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease—the major protagonists of NDs—while briefly covering other NDs such as amyotrophic lateral sclerosis, multiple sclerosis, and prion diseases. Melatonin selectively accumulates in neuronal mitochondria and exerts neuroprotection through multiple pathways: (1) direct scavenging of reactive oxygen species (ROS); (2) transcriptional activation of antioxidant defenses via the SIRT3 and Nrf2 pathways; (3) regulation of mitochondrial dynamics through DRP1 and OPA1; and (4) promotion of PINK1- and Parkin-mediated mitophagy. Additionally, melatonin exhibits context-dependent pleiotropy: under conditions of mild mitochondrial stress, it restores mitochondrial homeostasis; under conditions of severe mitochondrial damage, it promotes pro-survival autophagy by inhibiting the PI3K/AKT/mTOR pathway, thereby conferring stage-specific therapeutic advantages. Overall, melatonin offers a sophisticated mitochondria-targeting strategy for the treatment of NDs. However, successful clinical translation requires clarification of receptor-dependent signaling pathways, development of standardized dosing strategies, and validation in large-scale randomized controlled trials. Full article
(This article belongs to the Special Issue Neurodegeneration: Pathways and Mechanisms)
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