Review synthesizing preclinical and some clinical evidence for repurposed drug classes (chemical chaperones, GLP‑1 receptor agonists, iron chelators, c‑Abl TKIs) across neurodegenerative diseases and proposing rational combinatory therapies to target multiple pathogenic mechanisms relevant to…

Offers a translational, repurposing-focused strategy to combine agents with complementary mechanisms and existing safety data, which could accelerate development of multi-target disease-modifying treatments for Parkinson’s disease.

We review the positive effects of several existing drugs from different classes, such as chemical chaperones, glucagon-like peptide-1 receptor agonists (GLP-1 RAs), iron chelators, and cluster-Abelson tyrosine kinase inhibitors (c-Abl TKIs), in preclinical disease models and in available published human data following use of these drugs in individuals with common neurodegenerative diseases (NDs), including Parkinson's disease (PD), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD). A concept of combinatory neuroprotective therapy using a drug-repurposing approach is then discussed. Finally, we propose a strategy to design an ideal combination of drugs able to address multiple pathogenic processes involved in neurodegeneration to achieve clinically meaningful results. ANN NEUROL 2026 ANN NEUROL 2026;99:1099-1112.