Decoding synaptic imbalance in neurodegenerative diseases: From pathological analysis to targeted intervention

Area of Science:

• Neuroscience
• Pathology
• Biochemistry

Background:

• Synapses are crucial for central nervous system (CNS) information processing.
• Synaptic dysfunction is an early indicator in neurodegenerative diseases, preceding neuronal death and clinical symptoms.
• Synaptic damage location and severity influence disease phenotypes and are linked to specific pathological proteins.

Purpose of the Study:

• To review current research on synaptic impairment in age-related neurodegenerative diseases.
• To detail location-specific synaptic damage in Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and Amyotrophic lateral sclerosis (ALS).
• To explore mechanisms driving synaptic dysfunction and potential therapeutic strategies.

Main Methods:

• Comprehensive literature review of synaptic impairment in neurodegenerative diseases.
• Analysis of pathological features and disease-related markers at synapses.
• Synthesis of five core mechanisms contributing to synaptic dysfunction.

Main Results:

• Synaptic impairment is a common early pathological feature in AD, PD, HD, and ALS.
• Specific pathological proteins are closely associated with synaptic dysfunction in each disease.
• Five key mechanisms identified: toxic protein effects, protein homeostasis disruption, excitotoxicity/calcium imbalance, oxidative stress/inflammation, and neurotrophic factor deficiency.

Conclusions:

• Synaptic dysfunction is a critical factor in the pathogenesis of age-related neurodegenerative diseases.
• Understanding these mechanisms can guide the development of biomarkers for early diagnosis.
• Targeted interventions addressing synaptic dysfunction hold promise for treating neurodegenerative diseases.