Precision Neurodegeneration: Integrating Molecular Mechanisms, Biomarkers, and Targeted Therapeutics - PubMed
5 hours ago
- #Biomarkers
- #Precision Medicine
- #Neurodegenerative Diseases
- Neurodegenerative diseases (NDDs) like Alzheimer's and Parkinson's are driven by protein misfolding, microglial responses, epigenetic dysregulation, and metabolic failure.
- Cryo-EM has identified distinct tau and α-synuclein strains linked to clinical phenotypes, aiding in precision diagnostics with over 90% accuracy.
- Single-cell transcriptomics highlight disease-associated microglia (DAM) and NLRP3 inflammasome as therapeutic targets, with TREM2 agonists and CSF1R modulators in phase II trials.
- Epigenetic changes are reversible drivers of synaptic failure, with CRISPR-dCas9 and HDAC inhibitors showing promise in restoring memory in mice.
- Metabolic interventions like ketone esters and time-restricted feeding improve mitochondrial quality control and reduce amyloid and tau pathology.
- Blood-based A/T/N algorithms and patient-specific genetics enable adaptive platform trials for personalized treatment strategies.
- Precision medicine for NDDs is now being operationalized in clinical pipelines, integrating molecular mechanisms, biomarkers, and targeted therapeutics.