[fusion_builder_container hundred_percent=”yes” overflow=”visible”][fusion_builder_row][fusion_builder_column type=”1_1″ background_position=”left top” background_color=”” border_size=”” border_color=”” border_style=”solid” spacing=”yes” background_image=”” background_repeat=”no-repeat” padding=”” margin_top=”0px” margin_bottom=”0px” class=”” id=”” animation_type=”” animation_speed=”0.3″ animation_direction=”left” hide_on_mobile=”no” center_content=”no” min_height=”none”][fusion_title size=”2″ content_align=”left” style_type=”” sep_color=”” margin_top=”” margin_bottom=”” class=”” id=””]GSK-3 and CNS[/fusion_title][fusion_text]Dysregulation of GSK-3 activity is believed to play a key role in the pathogenesis of CNS disorders. GSK-3 and its downstream pathways were shown to be tightly linked with signaling pathways regulating synaptic modulation, neuroprotection and neuroplasticity. Of particular relevance to neurodegenarative disorders, GSK-3 binds and / or phosphoryltes tau, presenilin-1, and collapsin response mediator protein, CRMP2, proteins that are implicated in the etiology of Alzheimer’s disease. Specifically, GSK-3 phosphorylates tau in most serine and threonine residues which are hyperphosphorylated in PHF (paired helical filament) in brains of Alzheimer’s patients. Subsequently, the phosphorylation of CRMP2 by GSK-3 affects neuroplasticity and axon grwoth. In addition, GSK-3 activity contributes to the production of Aβ peptide, the principal protein component of amyloid plaques, the hallmark of Alzheimer’s disease pathology. Furthermore, recent work suggested a mechanistic link between amyloid signaling and tauopathy via activation of GSK-3.

 [/fusion_text][/fusion_builder_column][fusion_builder_column type=”1_1″ background_position=”left top” background_color=”” border_size=”” border_color=”” border_style=”solid” spacing=”yes” background_image=”” background_repeat=”no-repeat” padding=”” margin_top=”0px” margin_bottom=”0px” class=”” id=”” animation_type=”” animation_speed=”0.3″ animation_direction=”left” hide_on_mobile=”no” center_content=”no” min_height=”none”][fusion_portfolio layout=”grid-with-text” picture_size=”fixed” boxed_text=”unboxed” filters=”no” columns=”2″ column_spacing=”12″ cat_slug=”gskcns” exclude_cats=”” number_posts=”4″ offset=”” excerpt_length=”35″ strip_html=”yes” carousel_layout=”title_on_rollover” scroll_items=”” autoplay=”no” show_nav=”yes” mouse_scroll=”no” animation_type=”fade” animation_direction=”down” animation_speed=”” class=”” id=””][/fusion_portfolio][fusion_text]Another important aspect in this regard is the contribution of GSK-3 to both inflammation and cell migration. Supportive evidence was also obtained from in vivo models. Thus, mice with conditional overexpression of brain-GSK-3 displayed hyperphosphorylation of tau, apoptotic neuronal cell death, and spatial learning deficit. On the other hand, reduced GSK-3 activity achieved either by pharmacological inhibitors or by genetic manipulations enhanced LTP (long term potentiation) and reversed the Alzheimer’s-like phenotype in vivo. These combined observations strongly suggest that GSK-3 activation is a critical step in brain aging and the cascade of detrimental events in Alzheimer’s disease pathology, and possibly in additional neurodegenerative disorders in which neuronal plasticity, cell migration, and/or LTP are hampered.

Learn more about GSK3 in Neuronal Plasticity and Neurodegeneration at Neuro.GSK-3 website.[/fusion_text][/fusion_builder_column][/fusion_builder_row][/fusion_builder_container]