title: Synaptic dysfunction and septin protein family members in neurodegenerative diseases.
abstract: Cognitive decline and disease progression in different neurodegenerative diseases typically involves synaptic dysfunction preceding the neuronal loss. The synaptic dysfunction is suggested to be caused by imbalanced synaptic plasticity i.e. enhanced induction of long-term depression and concomitantly decreased long-term potentiation accompanied with excess stimulation of extrasynaptic N-Methyl-D-aspartate (NMDA) receptors due to various disturbances in pre- and postsynaptic sites. Recent research has identified neurodegenerative disease-related changes in protein accumulation and aggregation, gene expression, and protein functions, which may contribute to imbalanced synaptic function. Nevertheless, a comprehensive understanding of the mechanisms regulating synaptic plasticity in health and disease is still lacking and therefore characterization of new candidates involved in these mechanisms is needed. Septins, a highly conserved group of guanosine-5'-triphosphate (GTP)-binding proteins, show high neuronal expression and are implicated in the regulation of synaptic vesicle trafficking and neurotransmitter release. In this review, we first summarize the evidence how synaptic dysfunction is related to the pathogenesis of Alzheimer's, Parkinson's and Huntington's disease and frontotemporal lobar degeneration. Then, we discuss different aspects of the potential involvement of the septin family members in the regulation of synaptic function in relation to the pathogenesis of neurodegenerative diseases.
authors.affiliation: Institute of Biomedicine, University of Eastern Finland, P.O. Box 1627, 70211, Kuopio, Finland. mikael.marttinen@uef.fi.|Institute of Clinical Medicine - Neurology, University of Eastern Finland, Kuopio, Finland. mikael.marttinen@uef.fi.|Department of Neurology, Kuopio University Hospital, Kuopio, Finland. mikael.marttinen@uef.fi.
authors.forename: Mikael
authors.initials: M
authors.lastname: Marttinen
authors.affiliation: Institute of Biomedicine, University of Eastern Finland, P.O. Box 1627, 70211, Kuopio, Finland. kaisa.kurkinen@uef.fi.|Institute of Clinical Medicine - Neurology, University of Eastern Finland, Kuopio, Finland. kaisa.kurkinen@uef.fi.|Department of Neurology, Kuopio University Hospital, Kuopio, Finland. kaisa.kurkinen@uef.fi.
authors.forename: Kaisa Ma
authors.initials: KM
authors.lastname: Kurkinen
authors.affiliation: Institute of Clinical Medicine - Neurology, University of Eastern Finland, Kuopio, Finland. Hilkka.Soininen@kuh.fi.|Department of Neurology, Kuopio University Hospital, Kuopio, Finland. Hilkka.Soininen@kuh.fi.
authors.forename: Hilkka
authors.initials: H
authors.lastname: Soininen
authors.affiliation: Institute of Clinical Medicine - Neurology, University of Eastern Finland, Kuopio, Finland. annakaisa.haapasalo@uef.fi.|Department of Neurology, Kuopio University Hospital, Kuopio, Finland. annakaisa.haapasalo@uef.fi.
authors.forename: Annakaisa
authors.initials: A
authors.lastname: Haapasalo
authors.affiliation: Institute of Biomedicine, University of Eastern Finland, P.O. Box 1627, 70211, Kuopio, Finland. mikko.hiltunen@uef.fi.|Institute of Clinical Medicine - Neurology, University of Eastern Finland, Kuopio, Finland. mikko.hiltunen@uef.fi.|Department of Neurology, Kuopio University Hospital, Kuopio, Finland. mikko.hiltunen@uef.fi.
authors.forename: Mikko
authors.initials: M
authors.lastname: Hiltunen
mesh_terms: D000818:Animals; D006801:Humans; D017774:Long-Term Potentiation; D019636:Neurodegenerative Diseases / Q000378:metabolism* / Q000473:pathology; D009473:Neuronal Plasticity / Q000502:physiology*; D058112:Septins / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: D058112:Septins