scholarly journals Structure-based discovery and bio-evaluation of a cyclopenta[4,5]thieno[2,3-d]pyrimidin-4-one as a phosphodiesterase 10A inhibitor

RSC Advances ◽  
2022 ◽  
Vol 12 (3) ◽  
pp. 1576-1591
Author(s):  
Mayasah Al-Nema ◽  
Anand Gaurav ◽  
Vannajan Sanghiran Lee ◽  
Baskaran Gunasekaran ◽  
Ming Tatt Lee ◽  
...  
Keyword(s):  
Neurodegenerative Disorders ◽  
Therapeutic Target ◽  
Potential Therapeutic Target ◽  
Phosphodiesterase 10A

Phosphodiesterase10A (PDE10A) is a potential therapeutic target for the treatment of several neurodegenerative disorders.

scholarly journals Selective autophagy as a potential therapeutic target for neurodegenerative disorders

2018 ◽  
Vol 17 (9) ◽  
pp. 802-815 ◽  
Author(s):  
Aurora Scrivo ◽  
Mathieu Bourdenx ◽  
Olatz Pampliega ◽  
Ana Maria Cuervo
Keyword(s):  
Neurodegenerative Disorders ◽  
Therapeutic Target ◽  
Potential Therapeutic Target ◽  
Selective Autophagy

IRAK4 Inhibition Attenuates Interleukin‐1‐Induced Astrogliosis: A Potential Therapeutic Target for Neurodegenerative Disorders?

2020 ◽  
Vol 34 (S1) ◽  
pp. 1-1
Author(s):  
Evan L. Reeder ◽  
Sean M. Collins ◽  
Poornima Gopalan ◽  
Sophia V. Norman ◽  
Christopher J. O'Connell ◽  
...  
Keyword(s):  
Neurodegenerative Disorders ◽  
Therapeutic Target ◽  
Interleukin 1 ◽  
Potential Therapeutic Target

scholarly journals Decreased kinesin-1 mitigates NMDA-induced exicitotoxicity and ischemia-evoked neurodegeneration

2018 ◽  
Author(s):  
Raozhou Lin ◽  
Zhigang Duan ◽  
Haitao Sun ◽  
Man-Lung Fung ◽  
Hansen Chen ◽  
...  
Keyword(s):  
Heavy Chain ◽  
Neural Activity ◽  
Neurodegenerative Disorders ◽  
Therapeutic Target ◽  
Molecular Mechanisms ◽  
Potential Therapeutic Target ◽  
Aspartate Receptor ◽  
Cytoplasmic Tails ◽  
Direct Binding ◽  
Activity Dependent

AbstractN-methyl-D-aspartate receptor (NMDAR) is highly compartmentalized in neurons and the dysfunction has been implicated in various neuropsychiatric and neurodegenerative disorders. Recent failure to exploit NMDAR antagonization as a potential therapeutic target has driven the need to identify molecular mechanisms that regulate NMDAR compartmentalization. Here, we report that neural activity-dependent reduction of Kif5b, the heavy chain of kinesin-1, protected neurons against NMDA-induced excitotoxicity and ischemia-provoked neurodegeneration. Direct binding of Kinesin-1 to the GluN2B cytoplasmic tails regulated levels of NMDAR at extrasynaptic sites and the subsequent influx of calcium mediated by extrasynaptic NMDAR via regulating the insertion of NMDARs into neuronal surface. Transient increase of Kif5b restored the surface levels of NMDAR and the decreased neuronal susceptibility to NMDA-induced excitotoxicity. Our findings reveal that kinesin-1 regulates extrasynaptic NMDAR targeting and signaling, and the reduction of kinesin-1 could be regulated by neural activity and could be exploited to postpone or halt neurodegeneration.

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