神经保护
神经退行性变
黑质
致密部
氧化应激
KEAP1型
神经炎症
帕金森病
药理学
多巴胺能
生物
神经科学
炎症
医学
多巴胺
转录因子
生物化学
免疫学
内科学
疾病
基因
作者
Amritha Chakkittukandiyil,Deepak Vasudevan Sajini,Arjunan Karuppaiah,Divakar Selvaraj
标识
DOI:10.1016/j.neuint.2022.105325
摘要
Parkinson's disease (PD) is a progressive neurodegenerative disorder. PD is associated with the loss of dopaminergic neurons in the substantia nigra pars compacta region of the midbrain. Present therapies for PD provide only symptomatic relief by restoring the dopamine (DA) level. However, they are not disease modifying agents and so they do not delay the disease progression. Alpha-synuclein aggregation, oxidative stress, mitochondrial dysfunction and chronic inflammation are considered to be the major pathological mechanisms mediating neurodegeneration in PD. To resist oxidative stress, the human body has an antioxidant defence mechanism consisting of many antioxidants and cytoprotective genes. The expression of those genes are largely controlled by the Kelch-like ECH-associated protein 1/Nuclear factor - erythroid - 2 - related factor 2/Antioxidant response element (Keap1/Nrf2/ARE) signalling pathway. The transcription factor Nrf2 is activated in response to oxidative or electrophilic stress and protects the cells from oxidative stress and inflammation. Nrf2 has been widely considered as a therapeutic target for neurodegeneration and several drugs are now being tested in clinical trials. Regulation of the Keap1/Nrf2/ARE pathway by small molecules which can act as Nrf2 activators could be effective for treating oxidative stress and neuroinflammation in PD. In this review, we had discussed the principal molecular mechanisms behind the neuroprotective effects of Keap1/Nrf2/ARE pathway in PD. Additionally, we also discussed the small molecules and phytochemicals that could activate the Nrf2 mediated anti-oxidant pathway for neuroprotection in PD.
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