Cholinergic deficiency involved in vascular dementia: possible mechanism and strategy of treatment.
Vascular dementia (VaD) is a progressive neurodegenerative disease with a high prevalence. Several studies have recently reported that VaD patients present cholinergic deficits in the brain and cerebrospinal fluid (CSF) that may be closely related to the pathophysiology of cognitive impairment. Moreover, cholinergic therapies have shown promising effects on cognitive improvement in VaD patients. The precise mechanisms of these cholinergic agents are currently not fully understood; however, accumulating evidence indicates that these drugs may act through the cholinergic anti-inflammatory pathway, in which the efferent vagus nerve signals suppress pro-inflammatory cytokine release and inhibit inflammation, although regulation of oxidative stress and energy metabolism, alleviation of apoptosis may also be involved. In this paper, we provide a brief overview of the cholinergic treatment strategy for VaD and its relevant mechanisms of anti-inflammation.Acta Pharmacologica Sinica (2009) 30: 879-888; doi: 10.1038/aps.2009.82.
Wang
Juan
J
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Zhang
Hai-Yan
HY
Tang
Xi-Can
XC
D000109:Acetylcholine / Q000172:deficiency*; D000470:Alkaloids; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D018678:Cholinergic Agents / Q000627:therapeutic use*; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D015140:Dementia, Vascular / Q000188:drug therapy* / Q000453:epidemiology / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D000077265:Donepezil; D005702:Galantamine / Q000627:therapeutic use; D006801:Humans; D007189:Indans / Q000627:therapeutic use; D007249:Inflammation / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy; D018696:Neuroprotective Agents / Q000627:therapeutic use; D018697:Nootropic Agents / Q000627:therapeutic use; D048448:Phenylcarbamates / Q000627:therapeutic use; D010880:Piperidines / Q000627:therapeutic use; D011950:Receptors, Cholinergic / Q000378:metabolism; D000068836:Rivastigmine; D012717:Sesquiterpenes / Q000627:therapeutic use; D015398:Signal Transduction / Q000502:physiology
D000470:Alkaloids; D000893:Anti-Inflammatory Agents; D018678:Cholinergic Agents; D002800:Cholinesterase Inhibitors; D007189:Indans; D018696:Neuroprotective Agents; D018697:Nootropic Agents; D048448:Phenylcarbamates; D010880:Piperidines; D011950:Receptors, Cholinergic; D012717:Sesquiterpenes; C050426:huperzine A; D005702:Galantamine; D000077265:Donepezil; D000109:Acetylcholine; D000068836:Rivastigmine