Molecular Mechanism in the Pathogenesis of Alzheimer’s Disease and Related Neurodegenerative Diseases

Dear Colleagues,

Alzheimer’s disease (AD) and related neurodegenerative disorders are complex conditions with intricate molecular underpinnings. AD often shares pathological features with other neurodegenerative diseases, including Parkinson’s disease, Huntington’s disease, and amyotrophic lateral sclerosis. Common mechanisms include protein misfolding, aggregation, and accumulation, leading to the formation of characteristic pathological structures, such as amyloid plaques and neurofibrillary tangles. In AD, pathogenesis involves multiple interconnected mechanisms. The aggregation of amyloid-β (Aβ) peptides and the formation of neurofibrillary tangles due to hyperphosphorylated tau proteins lead to synaptic dysfunction and neuronal loss. Additionally, the dysregulation of calcium homeostasis, oxidative stress, and mitochondrial dysfunction contribute to pathogenesis. Emerging evidence suggests the involvement of inflammation, where microglial activation and astrocytic response perpetuate neuronal damage.

Moreover, dysfunctions in proteostasis, including impaired autophagy and ubiquitin-proteasome system activity, contribute to the accumulation of misfolded proteins, exacerbating neurodegeneration. Aberrant lipid metabolism and disrupted signaling cascades, such as the Wnt and insulin signaling pathways, further contribute to disease progression. Furthermore, genetic predisposition, including the role of apolipoprotein E (APOE) alleles, plays a crucial role in disease susceptibility.

Understanding these intricate molecular mechanisms holds promise for the development of targeted therapeutic interventions, such as Aβ aggregation inhibitors, tau-directed therapies, anti-inflammatory agents, and modulators of proteostasis. Integrative research efforts are needed to unravel the complex interplay between these mechanisms and to develop effective strategies for the prevention and treatment of Alzheimer's Disease and related neurodegenerative disorders.

Dr. Kun Zou
Guest Editor

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• Alzheimer’s disease
• neurodegenerative diseases
• Parkinson’s disease
• amyotrophic lateral sclerosis
• molecular mechanism
• neuronal death
• amyloid beta-protein
• Tau
• alpha-synuclein
• TDP43