The Potential Use of Matrix Metalloproteinases in Alzheimer’s Disease Therapy

TL;DR

This paper reviews how matrix metalloproteinases (MMPs) could be used in new Alzheimer’s disease therapies, as they have both helpful and harmful effects in the disease.

Contribution

The paper provides a novel synthesis of how MMPs may be therapeutically modulated in Alzheimer’s disease based on their dual roles.

Findings

MMPs can degrade amyloid but also contribute to blood–brain barrier disruption.

Their roles are context-dependent, which may explain past therapy failures.

Selective modulation of MMPs could lead to better Alzheimer’s treatments.

Abstract

Alzheimer’s disease is the most common cause of dementia and one of the greatest challenges of current medicine. Its pathophysiology is complex, involving β-amyloid deposition, tau hyperphosphorylation, chronic neuroinflammation, and progressive neuronal loss. Despite the introduction of novel therapies, treatment efficacy remains limited, prompting the search for alternative therapeutic targets. One promising area of research focuses on matrix metalloproteinases-proteolytic enzymes involved in tissue remodeling, synaptic plasticity, and inflammatory responses. In the context of AD, MMPs may exert both protective effects, through amyloid degradation, and detrimental effects such as blood–brain barrier disruption and amplification of neuroinflammatory damage. Understanding the dual and context-dependent roles of MMPs may help explain past translational failures and enable the development of more selective, stage-dependent therapeutic strategies. This article is a narrative review summarizing current evidence on the roles of MMPs in AD, with a particular focus on their therapeutic modulation and potential implications for future clinical research. Insights into MMP biology may ultimately guide the design of interventions with improved efficacy and safety for patients with AD.

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