Recent research indicates that Munc18-1, a protein traditionally associated with synaptic transmission, also plays roles in APP processing, vesicle fusion, and interacts with proteins like phospholipase D, alpha-synuclein, and CDK5, linking it to various dementia-related pathological features.

Alterations in Munc18-1 levels in critical brain regions such as the hippocampus and cortex are linked to impaired synaptic function, neuroinflammation, and neuronal loss, highlighting its potential as a therapeutic target.

Munc18-1 influences neuroinflammatory responses and regulates the release of brain-derived neurotrophic factor (BDNF), both of which are vital in aging and neurodegenerative processes.

As a brain-enriched protein essential for membrane fusion and synaptic vesicle exocytosis, Munc18-1 levels are found to be reduced in the brains of dementia patients, underscoring its importance in maintaining neural health.

Dementia involves complex pathological mechanisms such as amyloid-beta deposition, Tau hyperphosphorylation, alpha-synuclein aggregation, neuroinflammation, oxidative stress, and synaptic dysfunction.

The main causes of dementia include neurodegenerative diseases like Alzheimer's and Lewy body dementia, along with potentially reversible conditions such as vascular injury, metabolic imbalances, infections, and toxins.

Dementia affects roughly 7% of individuals over 65 worldwide, with higher prevalence in countries with longer life expectancy, reflecting its status as a major aging-related health issue.

Given the multifactorial nature of dementia, current therapies have limited efficacy, making multi-target strategies and combination therapies more promising than single-agent approaches.

Considering Munc18-1's multifaceted roles, modulating its activity could offer a novel therapeutic avenue for addressing the complex pathology of dementia, warranting further research into its mechanisms.