神经炎症
小胶质细胞
炎症
促炎细胞因子
神经退行性变
PI3K/AKT/mTOR通路
药理学
医学
免疫学
信号转导
生物
细胞生物学
内科学
疾病
作者
Rishika Dhapola,Subhendu Shekhar Hota,Phulen Sarma,Anusuya Bhattacharyya,Bikash Medhi,Dibbanti Harikrishna Reddy
标识
DOI:10.1007/s10787-021-00889-6
摘要
Alzheimer’s disease (AD) is a major contributor of dementia leading to the degeneration of neurons in the brain with major symptoms like loss of memory and learning. Many evidences suggest the involvement of neuroinflammation in the pathology of AD. Cytokines including TNF-α and IL-6 are also found increasing the BACE1 activity and expression of NFκB resulting in generation of Aβ in AD brain. Following the interaction of Aβ with microglia and astrocytes, other inflammatory molecules also get translocated to the site of inflammation by chemotaxis and exaggerate neuroinflammation. Various pathways like NFκB, p38 MAPK, Akt/mTOR, caspase, nitric oxide and COX trigger microglia to release inflammatory cytokines. PPARγ agonists like pioglitazone increases the phagocytosis of Aβ and reduces inflammatory cytokine IL-1β. Celecoxib and roficoxib like selective COX-2 inhibitors also ameliorate neuroinflammation. Non-selective COX inhibitor indomethacin is also potent inhibitor of inflammatory mediators released from microglia. Mitophagy process is considered quite helpful in reducing inflammation due to microglia as it promotes the phagocytosis of over activated microglial cells and other inflammatory cells. Mitophagy induction is also beneficial in the removal of damaged mitochondria and reduction of infiltration of inflammatory molecules at the site of accumulation of the damaged mitochondria. Targeting these pathways and eventually ameliorating the activation of microglia can mitigate neuroinflammation and come out as a better therapeutic option for the treatment of Alzheimer’s disease.
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