Metalloproteinases and their tissue inhibitors in Alzheimer’s disease and other neurodegenerative disorders

As life expectancy increases worldwide, age-related neurodegenerative diseases will increase in parallel. The lack of effective treatment strategies may soon lead to an unprecedented health, social and economic crisis. Any attempt to halt the progression of these diseases requires a thorough knowled...

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Published inCellular and molecular life sciences : CMLS Vol. 76; no. 16; pp. 3167 - 3191
Main Authors Rivera, Santiago, García-González, Laura, Khrestchatisky, Michel, Baranger, Kévin
Format Journal Article
LanguageEnglish
Published Cham Springer International Publishing 01.08.2019
Springer Nature B.V
Springer Verlag
Subjects
ADAM protein
ADAM Proteins - metabolism
Age
Alzheimer Disease - metabolism
Alzheimer Disease - pathology
Amyloid beta-Peptides - metabolism
Amyloid beta-Protein Precursor - metabolism
Amyotrophic lateral sclerosis
Biochemistry
Biochemistry, Molecular Biology
Biomedical and Life Sciences
Biomedicine
Brain
Cell Biology
Disease
Disruption
Economic crisis
Humans
Huntington Disease - metabolism
Huntington Disease - pathology
Inflammation
Inhibitors
Life expectancy
Life Sciences
Life span
Matrix metalloproteinase
Matrix metalloproteinases
Matrix Metalloproteinases - metabolism
Medical innovations
Neurodegenerative diseases
Neurodegenerative Diseases - metabolism
Neurodegenerative Diseases - pathology
Neurological diseases
Neurons and Cognition
Parkinson Disease - metabolism
Parkinson Disease - pathology
Parkinson's disease
Protein folding
Proteinase
Review
Scaffolding
Target recognition
Therapeutic applications
Thrombospondin
Tissue inhibitor of metalloproteinases
Tissue Inhibitor of Metalloproteinases - metabolism
ADAM
Amyotrophic lateral sclerosis
Huntington’s disease
Neurodegenerative brain disease
Parkinson’s disease
TIMP
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Abstract As life expectancy increases worldwide, age-related neurodegenerative diseases will increase in parallel. The lack of effective treatment strategies may soon lead 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.
AbstractList As life expectancy increases worldwide, age-related neurodegenerative diseases will increase in parallel. The lack of effective treatment strategies may soon lead 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.
As life expectancy increases worldwide, age-related neurodegenerative diseases will increase in parallel. The lack of effective treatment strategies may soon lead 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.
Author García-González, Laura
Baranger, Kévin
Rivera, Santiago
Khrestchatisky, Michel
Author_xml – sequence: 1
  givenname: Santiago
  orcidid: 0000-0001-6649-2712
  surname: Rivera
  fullname: Rivera, Santiago
  email: santiago.rivera@univ-amu.fr
  organization: Aix-Marseille Univ, CNRS, INP, Inst Neurophysiopathol
– sequence: 2
  givenname: Laura
  surname: García-González
  fullname: García-González, Laura
  organization: Aix-Marseille Univ, CNRS, INP, Inst Neurophysiopathol
– sequence: 3
  givenname: Michel
  surname: Khrestchatisky
  fullname: Khrestchatisky, Michel
  organization: Aix-Marseille Univ, CNRS, INP, Inst Neurophysiopathol
– sequence: 4
  givenname: Kévin
  surname: Baranger
  fullname: Baranger, Kévin
  organization: Aix-Marseille Univ, CNRS, INP, Inst Neurophysiopathol
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Issue 16
Keywords ADAM
Amyotrophic lateral sclerosis
Huntington’s disease
Neurodegenerative brain disease
Parkinson’s disease
TIMP
Language English
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PublicationTitle Cellular and molecular life sciences : CMLS
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Snippet As life expectancy increases worldwide, age-related neurodegenerative diseases will increase in parallel. The lack of effective treatment strategies may...
As life expectancy increases worldwide, age-related neurodegenerative diseases will increase in parallel. The lack of effective treatment strategies may soon...
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SubjectTerms ADAM protein
ADAM Proteins - metabolism
Age
Alzheimer Disease - metabolism
Alzheimer Disease - pathology
Amyloid beta-Peptides - metabolism
Amyloid beta-Protein Precursor - metabolism
Amyotrophic lateral sclerosis
Biochemistry
Biochemistry, Molecular Biology
Biomedical and Life Sciences
Biomedicine
Brain
Cell Biology
Disease
Disruption
Economic crisis
Humans
Huntington Disease - metabolism
Huntington Disease - pathology
Inflammation
Inhibitors
Life expectancy
Life Sciences
Life span
Matrix metalloproteinase
Matrix metalloproteinases
Matrix Metalloproteinases - metabolism
Medical innovations
Neurodegenerative diseases
Neurodegenerative Diseases - metabolism
Neurodegenerative Diseases - pathology
Neurological diseases
Neurons and Cognition
Parkinson Disease - metabolism
Parkinson Disease - pathology
Parkinson's disease
Protein folding
Proteinase
Review
Scaffolding
Target recognition
Therapeutic applications
Thrombospondin
Tissue inhibitor of metalloproteinases
Tissue Inhibitor of Metalloproteinases - metabolism
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Title Metalloproteinases and their tissue inhibitors in Alzheimer’s disease and other neurodegenerative disorders
URI https://link.springer.com/article/10.1007/s00018-019-03178-2
https://www.ncbi.nlm.nih.gov/pubmed/31197405
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https://www.proquest.com/docview/2261966400
https://hal.science/hal-02407337
https://pubmed.ncbi.nlm.nih.gov/PMC11105182
Volume 76
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