PAR-1 in Alzheimer's Disease: Pathophysiological Insights and Mechanistic Perspectives - PubMed
8 hours ago
- #Alzheimer's Disease
- #PAR-1
- #Neurodegeneration
- PAR-1, a G protein-coupled receptor activated by thrombin, plays a complex role in Alzheimer's disease (AD).
- AD is marked by amyloid-β accumulation, neuroinflammation, tau hyperphosphorylation, and synaptic dysfunction.
- PAR-1 activation exacerbates neuroinflammation and Aβ pathology but also protects synaptic plasticity.
- In preclinical models, PAR-1 inhibition improves cognitive deficits and reduces Aβ accumulation.
- PAR-1 activation promotes tau hyperphosphorylation and neurofibrillary tangle formation, leading to synaptic loss and cognitive decline.
- PAR-1 increases blood-brain barrier permeability, allowing toxic substances to enter the brain and worsen neurodegeneration.
- No clinical trials have directly targeted PAR-1 in AD, despite strong preclinical evidence.
- Potential therapeutic strategies include repurposing existing PAR-1 inhibitors for AD treatment.
- PAR-1's dual roles highlight the need for multitarget approaches to address AD's multifactorial pathophysiology.