title: Microglial voltage-gated sodium channels modulate cellular response in Alzheimer's disease--a new perspective on an old problem.
abstract: Alzheimer's disease (AD) determines gradual loss of cognition and memory function, eventually leading to clinical manifest dementia. The pathogenic mechanisms of AD remain elusive and treatment options unsatisfactory, targeting only symptoms like memory loss, behavior changes, sleep disorders and seizures. These therapies are not stopping the disease's progression, at their best they can only delay it. Accumulating evidence suggests that AD is associated with a microglial dysfunction. Microglia are resident immune cells that provide continuous surveillance within the brain. When excessively activated, microglial response can also have detrimental effects via the exacerbation of inflammatory processes and release of neurotoxic substances. Recently, it was recognized that microglia express voltage-gated ion channels, in particularly voltage-gated sodium channels (VGSC). Pharmacological block of VGSC has been attempted symptomatically in AD to control the epileptic features often associated with AD, as well as to relieve detrimental behavioral and psychological symptoms of dementia. The success of VGSC treatment in AD was unexpectedly variable, ranging from very beneficial to plain detrimental. This variability could not be satisfactorily explained solely by the neuronal effects. This article will try to discuss possible implication of microglial VGSC dysfunction in AD according to available data, own personal experience of the authors and propose a new way to investigate its possible implications.
authors.affiliation: Center of Clinical and Experimental Medicine, University of Medicine and Pharmacy of Craiova, Romania; bogdan.catalin@webmail.umfcv.ro.
authors.forename: Bogdan
authors.initials: B
authors.lastname: Cătălin
authors.forename: Smaranda
authors.initials: S
authors.lastname: Mitran
authors.forename: Mihai
authors.initials: M
authors.lastname: Ciorbagiu
authors.forename: Eugen
authors.initials: E
authors.lastname: Osiac
authors.forename: Tudor Adrian
authors.initials: TA
authors.lastname: Bălşeanu
authors.forename: LaurenŢiu
authors.initials: L
authors.lastname: Mogoantă
authors.forename: Sorin Nicolae
authors.initials: SN
authors.lastname: Dinescu
authors.forename: Carmen Valeria
authors.initials: CV
authors.lastname: Albu
authors.forename: Cecil Sorin
authors.initials: CS
authors.lastname: Mirea
authors.forename: Ionică Daniel
authors.initials: ID
authors.lastname: Vîlcea
authors.forename: Maria
authors.initials: M
authors.lastname: Iancău
authors.forename: Veronica
authors.initials: V
authors.lastname: Sfredel
mesh_terms: D000375:Aging; D000544:Alzheimer Disease / Q000378:metabolism*; D000682:Amyloid / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000473:pathology; D018450:Disease Progression; D005786:Gene Expression Regulation; D006801:Humans; D007107:Immune System; D007249:Inflammation; D051379:Mice; D017628:Microglia / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000503:physiopathology; D012640:Seizures / Q000150:complications; D061566:Voltage-Gated Sodium Channels / Q000378:metabolism*
chemical_list: D000682:Amyloid; D061566:Voltage-Gated Sodium Channels