Browsing by Author "Hota, Subhendu Shekhar"

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    Recent advances in molecular pathways and therapeutic implications targeting neuroinflammation for Alzheimer�s disease
    (Springer Science and Business Media Deutschland GmbH, 2021-11-23T00:00:00) Dhapola, Rishika; Hota, Subhendu Shekhar; Sarma, Phulen; Bhattacharyya, Anusuya; Medhi, Bikash; Reddy, Dibbanti HariKrishna
    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-? and IL-6 are also found increasing the BACE1 activity and expression of NF?B resulting in generation of A? in AD brain. Following the interaction of A? with microglia and astrocytes, other inflammatory molecules also get translocated to the site of inflammation by chemotaxis and exaggerate neuroinflammation. Various pathways like NF?B, p38 MAPK, Akt/mTOR, caspase, nitric oxide and COX trigger microglia to release inflammatory cytokines. PPAR? agonists like pioglitazone increases the phagocytosis of A? and reduces inflammatory cytokine IL-1?. 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. � 2021, The Author(s), under exclusive licence to Springer Nature Switzerland AG.