MMP-9 Inhibitor GM6001 Prevents the Development of ssTBI-Induced Parkinson's Disease via the Autophagy Pathway.
Chao LinWei WuHua LuWentao LiZhongyuan BaoYingyi WangLin ZhaoTianwei GuoNing CaiZheng LiJing JiLijun HouYongping YouNing LiuPublished in: Cellular and molecular neurobiology (2020)
Concussion is a widely recognized environmental risk factor for neurodegenerative diseases, including Parkinson's disease (PD). Small-vessel disease of the brain has been reported to contribute to neurodegenerative diseases. In this study, we observed BBB disruption in wild-type (WT) mice, but not in matrix metalloproteinase 9 (MMP-9) knockout mice, subjected to single severe traumatic brain injury (ssTBI). Furthermore, treating ssTBI mice with the MMP-9 inhibitor GM6001 effectively maintained BBB integrity, promoted the elimination of damaged mitochondria via mitophagy, and then prevented neuronal death and progressive neurodegeneration. However, we did not observe this neuroprotective effect of MMP-9 inhibition in beclin-1-/+ mice. Collectively, these findings revealed that concussion led to BBB disruption via MMP-9, and that GM6001 prevented the development of PD via the autophagy pathway.
Keyphrases
- wild type
- blood brain barrier
- cell migration
- cell death
- severe traumatic brain injury
- high fat diet induced
- cerebral ischemia
- signaling pathway
- oxidative stress
- endoplasmic reticulum stress
- multiple sclerosis
- traumatic brain injury
- type diabetes
- diabetic rats
- subarachnoid hemorrhage
- high glucose
- adipose tissue
- drug induced
- mouse model
- brain injury
- skeletal muscle
- functional connectivity