Molecular Mechanisms and Novel Therapeutic Approaches of Neurodegenerative Diseases

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Biological Factors".

Deadline for manuscript submissions: 31 August 2025 | Viewed by 843

Special Issue Editor

Special Issue Information

Dear Colleagues,

Neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis (ALS), represent a growing global health challenge, affecting millions and leading to significant morbidity and mortality. These conditions are characterized by progressive neuronal loss and the deterioration of critical brain functions, often resulting in memory impairment, motor dysfunction, and a decline in cognitive and physical abilities. Despite substantial advances in understanding the pathophysiology of these disorders, effective disease-modifying therapies remain elusive.

Recent insights into the molecular mechanisms underlying neurodegenerative diseases have opened new avenues for therapeutic exploration. Key areas of focus include the accumulation of misfolded proteins, mitochondrial dysfunction, oxidative stress, neuroinflammation, and genetic mutations that drive disease pathology. Understanding these complex and often interconnected pathways has catalyzed the development of novel approaches, including gene therapy, RNA-based therapies, small-molecule inhibitors, and immunotherapy.

This Special Issue, "Molecular Mechanisms and Novel Therapeutic Approaches of Neurodegenerative Diseases", aims to gather pioneering research that explores these molecular underpinnings and innovative treatment strategies. We welcome studies that delve into cellular pathways involved in disease progression, as well as translational research efforts focused on developing targeted and personalized therapies. By addressing challenges such as drug delivery across the blood–brain barrier, off-target effects, and long-term efficacy, this Issue aspires to drive forward the search for effective treatments, providing hope for patients and families affected by neurodegenerative disorders.

Dr. Zhidong Zhou
Guest Editor

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Keywords

  • neurodegenerative disease
  • therapeutic approaches
  • molecular mechanisms
  • RNA-based therapies
  • gene therapy
  • small-molecule inhibitors
  • immunotherapy

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Published Papers (1 paper)

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10 pages, 2756 KiB  
Brief Report
Enhancing Membrane Repair Using Recombinant MG53/TRIM72 (rhMG53) Reduces Neurotoxicity in Alzheimer’s Disease Models
by Hannah R. Bulgart, Miguel A. Lopez Perez and Noah Weisleder
Biomolecules 2025, 15(3), 418; https://doi.org/10.3390/biom15030418 - 15 Mar 2025
Viewed by 634
Abstract
Alzheimer’s Disease (AD) is the most common neurodegenerative disease that involves neuronal cell death initiated by the breakdown of the plasma membrane. Amyloid beta (Aβ), a hallmark protein that contributes to AD pathogenesis, is known to interact directly with the plasma membrane and [...] Read more.
Alzheimer’s Disease (AD) is the most common neurodegenerative disease that involves neuronal cell death initiated by the breakdown of the plasma membrane. Amyloid beta (Aβ), a hallmark protein that contributes to AD pathogenesis, is known to interact directly with the plasma membrane and induce increased intracellular calcium levels, reactive oxygen species (ROS), and cell death. Our recent studies revealed that elevated levels of Aβ42 induce a plasma membrane repair defect in neurons that compromises this conserved cellular response that would normally repair the disruption. Here, we tested if recombinant MG53/TRIM72 protein (rhMG53), a therapeutic protein known to increase plasma membrane repair capacity, could enhance membrane repair in AD neurons. rhMG53 increased plasma membrane repair in ex vivo and in vitro tissue treated with Aβ42 or cerebrospinal fluid from AD patients, normalizing intracellular calcium levels, ROS, and cell death in treated cells. This study demonstrates that increasing plasma membrane repair can rescue neural cells from the neurotoxic effects of Aβ, indicating that elevating plasma membrane repair could be a viable therapeutic approach to reduce neuronal death in AD. Full article
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