Matrix metalloproteinases (MMPs) in neurodegenerative diseases, an updated overview of the role of MT1-MMP and MT5-MMP in Alzheimer's disease.

Neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and Huntington's disease, pose an increasing threat to global health due to ageing populations and the lack of effective treatments. Matrix metalloproteinases (MMPs), which are proteases that belong to the metzincin superfamily, are critical regulators of neuroinflammation, blood-brain barrier integrity, protein misfolding, synaptic dysfunction and neuronal death. This chapter provides a comprehensive overview of the roles of MMPs at the intersection of the molecular and cellular mechanisms that underpin neurodegenerative processes. The focus is on their pathophysiological mechanisms, therapeutic potential, and recent advances. We highlight novel mechanistic insights in Alzheimer's disease, such as the roles of MT1-MMP and MT5-MMP in amyloid-beta peptide production and the dual functions of MMPs in both neuroprotection and neurotoxicity. This review emphasizes the need for further mechanistic research into the different MMPs involved in neurodegenerative diseases.