Matrix Metalloproteinase Dynamics in Neurodegenerative Diseases

Matrix metalloproteinases (MMPs) orchestrate proteolytic and signalling events within the central nervous system and play pivotal roles in the initiation and progression of neurodegenerative disorders. By modulating extracellular matrix remodelling, influencing blood–brain barrier integrity and processing pathological proteins, MMPs contribute to hallmarks of Alzheimer’s, Parkinson’s, amyotrophic lateral sclerosis and other diseases. Dysregulated expression or activation of MMPs can lead to excessive degradation of matrix proteins, neuroinflammation, synaptic dysfunction and neuronal death. Conversely, certain MMPs participate in the clearance of amyloid-β and other toxic aggregates, illustrating their dualistic nature as both protectors and mediators of pathology. Understanding the spatio-temporal dynamics of MMP activity is crucial for elucidating disease mechanisms and developing targeted interventions.

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Matrix Metalloproteinase Dynamics in Neurodegenerative Diseases publication trend

The graph below shows the total number of articles in matrix metalloproteinase dynamics in neurodegenerative diseases across all publications each year (not limited to Nature Index journals).

Technical terms

Matrix metalloproteinases (MMPs): zinc-dependent endopeptidases that degrade extracellular matrix components and regulate signalling molecules in the central nervous system.

Tissue inhibitors of metalloproteinases (TIMPs): endogenous proteins that bind to MMPs and inhibit their proteolytic activity.

Amyloid precursor protein (APP): transmembrane protein whose proteolytic processing generates amyloid-β peptides associated with Alzheimer’s disease.

Amyloid-β (Aβ): peptide fragment derived from APP that aggregates into neurotoxic oligomers and plaques in Alzheimer’s pathology.

Blood–brain barrier (BBB): selective vascular interface that maintains central nervous system homeostasis by regulating molecular and cellular trafficking.

References

1. Decreased ratios of matrix metalloproteinases to tissue-type inhibitors in cerebrospinal fluid in sporadic and hereditary cerebral amyloid angiopathy. Alzheimer's Research & Therapy (2023).
2. The η-secretase-derived APP fragment ηCTF is localized in Golgi, endosomes and extracellular vesicles and contributes to Aβ production. Cellular and Molecular Life Sciences (2023).
3. Sex-specific associations of matrix metalloproteinases in Alzheimer’s disease. Biology of Sex Differences (2023).