Adenosine A2A Receptor Antagonists in Neurodegenerative Diseases: Huge Potential and Huge Challenges
نویسندگان
چکیده
منابع مشابه
Adenosine A2A Receptor Antagonists in Neurodegenerative Diseases: Huge Potential and Huge Challenges
In this opinion paper, we provide scientific-based reasons about the huge therapeutic potential of adenosine A2A receptor antagonists, and about the huge challenges to demonstrate efficacy in clinical trials, i.e., to provide data now required to approve a new medication by the regulatory bodies, such as U.S. Food and Drug Administration (FDA). Adenosine is an autacoid present in all tissue and...
متن کاملStriatal Pre- and Postsynaptic Profile of Adenosine A2A Receptor Antagonists
Striatal adenosine A(2A) receptors (A(2A)Rs) are highly expressed in medium spiny neurons (MSNs) of the indirect efferent pathway, where they heteromerize with dopamine D(2) receptors (D(2)Rs). A(2A)Rs are also localized presynaptically in cortico-striatal glutamatergic terminals contacting MSNs of the direct efferent pathway, where they heteromerize with adenosine A(1) receptors (A(1)Rs). It h...
متن کاملIdentification of Novel Adenosine A2A Receptor Antagonists by Virtual Screening
Virtual screening was performed against experimentally enabled homology models of the adenosine A(2A) receptor, identifying a diverse range of ligand efficient antagonists (hit rate 9%). By use of ligand docking and Biophysical Mapping (BPM), hits 1 and 5 were optimized to potent and selective lead molecules (11-13 from 5, pK(I) = 7.5-8.5, 13- to >100-fold selective versus adenosine A(1); 14-16...
متن کاملFluorinated Adenosine A2A Receptor Antagonists Inspired by Preladenant as Potential Cancer Immunotherapeutics
Antagonism of the adenosine A2A receptor on T cells blocks the hypoxia-adenosinergic pathway to promote tumor rejection. Using an in vivo immunoassay based on the Concanavalin A mouse model, a series of A2A antagonists were studied and identified preladenant as a potent lead compound for development. Molecular modeling was employed to assist drug design and subsequent synthesis of analogs and t...
متن کاملRole of Microglia Adenosine A2A Receptors in Retinal and Brain Neurodegenerative Diseases
Neuroinflammation mediated by microglial cells in the brain has been commonly associated with neurodegenerative diseases. Whether this microglia-mediated neuroinflammation is cause or consequence of neurodegeneration is still a matter of controversy. However, it is unequivocal that chronic neuroinflammation plays a role in disease progression and halting that process represents a potential ther...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
ژورنال
عنوان ژورنال: Frontiers in Psychiatry
سال: 2018
ISSN: 1664-0640
DOI: 10.3389/fpsyt.2018.00068