BiMe

Rethinking Alzheimer´s disease therapeutics: Synapses as prime targets

date
24.05.2018 
time
04:00 PM - 05:00 PM 
speaker
Prof. Roger Lefort 
affiliation
Columbia University Medical Center. Department of Pathology and Cell Biology, The Taub Institute for Research on Alzheimer's Disease and the Aging Brain 
language
en 
main topic
Biology: general
subtopics
Medicine: Regeneration
abstract

Abstract: Synaptic dysfunction and the loss of dendritic spines are invariable occurrences in Alzheimer’s disease (AD). Our research has implicated the Rho-family GTPases, RhoA and Rac1, as key mediator of the synaptotoxic effects of Abeta in neurons. RhoA and Rac1 play critical roles in regulating dendritic spines dynamics by regulating the actin cytoskeleton. RhoA and Rac1 have antagonistic effects: Rac1 favors the formation and stabilization of new spines, whereas RhoA blocks their sprouting and promotes their destabilization. This implies that an imbalance in RhoA/Rac1 signaling may have deleterious effects on dendritic maintenance. Consistent with this idea, our studies show that spine loss in neurons exposed to Aβ correlates with increased RhoA and decreased Rac1 activity. Moreover, blocking RhoA activity neurons completely abrogates the synaptotoxic effects of Aβ suggesting that RhoA may be a therapeutic target for AD.
5 most important publications:
Olabarria M, Corona C, Pasini S, Lefort R; Topoisomerase inhibitor type I topotecan reverses memory impairments in Alzheimer’s disease mouse model. J. Clin. Invest. (in review)
Olabarria M, Corona C, Robador P, Pasini S, Song C, Patel H, Lefort R; Dysfunction of the ubiquitin E3 ligase Ube3A/E6-AP contributes to synaptic pathophysiology in Alzheimer’s disease. Comm. Biol. (in press)
Yang J, Mandriota N, Harrellson SG, Molina JA, Yuste R, Lefort R., Sahin O., Synaptic elasticity. Nat. Neurosci. (in press)
†Pozueta J., †Lefort R., Ribe E., Troy, C., Arancio O., Shelanski M.; Caspase-2 mediates dendritic spine and behavioral alterations in J20 APP transgenic mice by regulating RhoA activity. Nat Commun. 2013;4:1939. †Pianu B., †Lefort R., Thuiliere L., Tabourier E., Bartolini F.; Amyloid beta1-42 peptide regulates microtubule stability independently of tau. J Cell Sci. 2014 Mar 1:127(Pt 5):1117-27

 

Last update: 22.05.2018 07:43.

venue 

DFG Center for Regenerative Therapies Dresden (CRTD, ground floor, auditorium left) 
Fetscherstraße 105
01307 Dresden
telefon
+49 (0)351 458 82064 
fax
+49 (0)351 458 82059  
e-mail
DFG Center for Regenerative Therapies Dresden 
homepage
http://www.crt-dresden.de 

organizer 

DFG Center for Regenerative Therapies Dresden (CRTD)
Fetscherstraße 105
01307 Dresden
telefon
+49 (0)351 458 82064 
fax
+49 (0)351 458 82059 
e-mail
DFG Center for Regenerative Therapies Dresden (CRTD) 
homepage
http://www.crt-dresden.de 
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