Kallikrein-related peptidase's significance in Alzheimer's disease pathogenesis: A comprehensive survey

Alzheimer's disease (AD) and related dementias constitute an important global health challenge. Detailed understanding of the multiple molecular mechanisms underlying their pathogenesis constitutes a clue for the management of the disease. Kallikrein-related peptidases (KLKs), a lead family of serine proteases, have emerged as potential biomarkers and therapeutic targets in the context of AD and associated cognitive decline. Hence, KLKs were proposed to display multifaceted impacts influencing various aspects of neurodegeneration, including amyloid-beta aggregation, tau pathology, neuroinflammation, and synaptic dysfunction. We propose here a comprehensive survey to summarize recent findings, providing an overview of the main kallikreins implicated in AD pathophysiology namely KLK8, KLK6 and KLK7. We explore the interplay between KLKs and key AD molecular pathways, shedding light on their significance as potential biomarkers for early disease detection. We also discuss their pertinence as therapeutic targets for disease-modifying interventions to develop innovative therapeutic strategies aimed at halting or ameliorating the progression of AD and associated dementias. [Display omitted] •Serine proteases among which kallikrein-related peptidases (KLK) are key players in AD patho-physiological pathways.•Some KLKs may serve as emerging biomarkers in combination with established ones such as Aβ and tau.•Some KLKs such as KLK6 and KLK8 were more extensively investigated and are discussed as potential therapeutical targets.