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您的检索式：作者名="Andrew Harkin"
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| 1 | Targeting the noradrenergic system for anti-inflammatory and neuroprotective effects: implications for Parkinson's disease显示文摘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. | Eoin O'Neill Andrew Harkin | 2018 | Neural Regeneration Research2018，13，8： | 5 |
| 2 | Poly I:C-induced activation of the immune response is accompanied by depression and anxiety-like behaviours, kynurenine pathway activation and reduced BDNF expression显示文摘 | Sinead M. Gibney Barry McGuinness Christine Prendergast Andrew Harkin Thomas J. Connor | 2012 | Brain Behavior and Immunity2012，，： | 1 |
| 3 | Regulation ofβ2-adrenoceptors in brain glia:implications for neuroinflammatory and degenerative disorders显示文摘Noradrenaline:Within the central nervous system(CNS),the primary source of the catecholamine neurotransmitter noradrenaline is the locus coeruleus(LC)in the pontine tegmentum,with LC neurons projecting to almost all regions of the brain and spinal cord.Following its release from LC neurons,noradrenaline has wide ranging effects.For example,noradrenaline is the endogenous agonist for G-coupledα-andβ-adrenoceptors that are expressed on many cell types,including neurons and glia,in both the peripheral nervous system and CNS.It is via these receptors that noradrenaline exerts its anti-inflammatory and neurotrophic effects in the brain.Noradrenaline additionally has adrenoceptor-independent neuroprotective actions,and as such plays a role in free radical scavenging and reducing oxidative stress(Feinstein et al.,2016). | Karen M.Ryan Andrew Harkin | 2020 | Neural Regeneration Research2020，15，11： | 0 |
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