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Matrix metalloproteinase (MMP) system in brain: identification and characterization of brain-specific MMP highly
Y Sekine-Aizawa1, E Hama, K Watanabe
1Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako-shi, Saitama, 351-0198 Japan.
Abstract:
The matrix metalloproteinase (MMP) family, comprising more than 20 isoforms, modulates the extracellular milieu by degrading extracellular matrix (ECM) proteins. Because MMP is one of the few groups of proteinases capable of hydrolysing insoluble fibrillar proteins, they are likely to play crucial roles in regulating both normal and pathophysiological processes in the brain. However, little is yet known about their possible neuronal functions due presumably to their unusual redundancy and to the absence of a complete catalogue of isoforms. As an initial step in understanding the MMP system in the brain, we analysed an expression spectrum of MMP in rat brain using RT-PCR and discovered a novel brain-specific MMP, MT5-MMP. MT5-MMP was the predominant species among the nongelatinase-type isoforms in brain. MT5-MMP, present in all brain tissues examined, was most strongly expressed in cerebellum and was localized in the membranous structures of expressing neurons, as assessed biochemically and immunohistochemically. In cerebellum, its expression was regulated developmentally and was closely associated with dendritic tree formation of Purkinje cells, suggesting that MT5-MMP may contribute to neuronal development. Furthermore, its stable postdevelopmental expression and colocalization with senile plaques in Alzheimer brain indicates possible roles in neuronal remodeling naturally occurring in adulthood and in regulating pathophysiological processes associated with advanced age.
Insights
Researchers discovered a novel brain-specific matrix metalloproteinase (MMP), MT5-MMP, crucial for neuronal development and potentially involved in brain aging and Alzheimer's disease.
Area of Science:
- Neuroscience
- Molecular Biology
- Biochemistry
Background:
- Matrix metalloproteinases (MMPs) are enzymes that degrade extracellular matrix proteins.
- MMPs play roles in normal and pathological brain processes, but their neuronal functions are poorly understood.
- A comprehensive understanding of MMP isoforms in the brain is lacking.
Purpose of the Study:
- To investigate the expression spectrum of MMPs in the rat brain.
- To identify novel MMPs with potential roles in brain function.
- To characterize the expression and localization of a newly discovered brain-specific MMP, MT5-MMP.
Main Methods:
- Reverse transcription polymerase chain reaction (RT-PCR) was used to analyze MMP expression.
- Biochemical and immunohistochemical methods were employed to assess MT5-MMP localization.
- Developmental expression patterns were studied in the cerebellum.
Main Results:
- A novel brain-specific MMP, MT5-MMP, was identified and found to be predominant among non-gelatinase MMPs in the brain.
- MT5-MMP was expressed in all brain tissues examined, with highest levels in the cerebellum.
- MT5-MMP localized to neuronal membranous structures and its expression correlated with Purkinje cell dendritic tree formation.
- MT5-MMP expression was stable post-developmentally and colocalized with senile plaques in Alzheimer's disease brains.
Conclusions:
- MT5-MMP is a novel brain-specific matrix metalloproteinase with significant roles in neuronal development.
- Its expression patterns suggest involvement in adult neuronal remodeling and age-related brain pathologies like Alzheimer's disease.