期刊
CELLULAR AND MOLECULAR LIFE SCIENCES
卷 76, 期 16, 页码 3167-3191出版社
SPRINGER BASEL AG
DOI: 10.1007/s00018-019-03178-2
关键词
Parkinson's disease; Huntington's disease; Amyotrophic lateral sclerosis; ADAM; TIMP; Neurodegenerative brain disease
资金
- CNRS
- Aix-Marseille Universite
- DHUNE Centre of Excellence
- Initiative d'Excellence of Aix-Marseille University - A*MIDEX, a French Investissements d'Avenir programme
- French National Research Agency (ANR), MAD5, second Investissements d'Avernir program
- French National Research Agency (ANR), PREVENTAD, second Investissements d'Avernir program
- CoEN
- Fondation Plan Alzheimer
- France Alzheimer
- Vaincre l'Alzheimer
As life expectancy increases worldwide, age-related neurodegenerative diseases will increasein parallel.The lack of effective treatment strategies may soonlead to an unprecedented health, social and economic crisis. Any attempt to halt the progression of these diseases requires a thorough knowledge of the pathophysiological mechanisms involved to facilitate the identification of new targets and the application of innovative therapeutic strategies. The metzincin superfamily of metalloproteinases includes matrix metalloproteinases (MMP), a disintegrin and metalloproteinase (ADAM) and ADAM with thrombospondin motifs (ADAMTS). These multigenic and multifunctional proteinase families regulate the functions of an increasing number of signalling and scaffolding molecules involved in neuroinflammation, blood-brain barrier disruption, protein misfolding, synaptic dysfunction or neuronal death. Metalloproteinases and their physiological inhibitors, the tissue inhibitors of metalloproteinases (TIMPs), are therefore, at the crossroads of molecular and cellular mechanisms that support neurodegenerative processes, and emerge as potential new therapeutic targets. We provide an overview of current knowledge on the role and regulation of metalloproteinases and TIMPs in four major neurodegenerative diseases: Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and Huntington's disease.
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