Targeting the noradrenergic system for anti-inflammatory and neuroprotective effects: implications for Parkinson's disease

查看全文 作　　者：Eoin O'[1]Neill;Andrew [1]Harkin

机构地区：[1]Neuropsychopharmacology Research Group, School of Pharmacy and Pharmaceutical Sciences & Trinity College Institute of Neuroscience, Trinity College

出　　处：《Neural Regeneration Research》索引2018年第13卷第8期,共6页

基　　金：Eoin O’Neill was supported by a Trinity College postgraduate award 摘　　要：Degeneration of the locus coeruleus noradrenergic system is thought to play a key role in the pathogenesis of Parkinson's disease(PD), whereas pharmacological approaches to increase noradrenaline bioavailability may provide neuroprotection. Noradrenaline inhibits microglial activation and suppresses pro-inflammatory mediator production(e.g., tumor necrosis factor-α, interleukin-1β & inducible nitric oxide synthase activity), thus limiting the cytotoxicity of midbrain dopaminergic neurons in response to an inflammatory stimulus. Neighbouring astrocyte populations promote a neurotrophic environment in response to β_2-adrenoceptor(β_2-AR) stimulation via the production of growth factors(e.g., brain derived neurotrophic factor, cerebral dopamine neurotrophic factor & glial cell derived neurotrophic factor which have shown promising neuroprotective and neuro-restorative effects in the nigrostriatal dopaminergic system. More recent findings have demonstrated a role for the β_2-AR in down-regulating expression levels of the human α-synuclein gene SNCA and relative α-synuclein protein abundance. Given that α-synuclein is a major protein constituent of Lewy body pathology, a hallmark neuropathological feature in Parkinson's disease, these findings could open up new avenues for pharmacological intervention strategies aimed at alleviating the burden of α-synucleinopathies in the Parkinsonian brain. In essence, the literature reviewed herein supports our hypothesis of a tripartite neuroprotective role for noradrenaline in combating PD-related neuropathology and motor dysfunction via(1) inhibiting nigral microglial activation & pro-inflammatory mediator production,(2) promoting the synthesis of neurotrophic factors from midbrain astrocytes and(3) downregulating α-synuclein gene expression and protein abundance in a β_2-AR-dependent manner. Thus, taken together, either pharmacologically enhancing extra-synaptic noradrenaline bioavailability or targeting glial β_2-ARs directly makes itself as a promising treatment option aimed at slowing/halting PD progression. 关键词：系统疾病指向蛋白质成分神经营养星形细胞调查结果生长因素

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Targeting the noradrenergic system for anti-inflammatory and neuroprotective effects: implications for Parkinson's disease

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