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Readable research linked to original sources
Browse normalized, publication-ready research with direct links to its evidence and source.
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Readable research linked to original sources
Browse normalized, publication-ready research with direct links to its evidence and source.
10 articles
Newest firstSynaptic plasticity is the key mechanism underlying learning and memory. Neurexins are pre-synaptic molecules that play a pivotal role in synaptic plasticity, interacting with many different post-synaptic molecules in the formation of neural circuits. Neurexins are alternatively spliced at different splice sites, yielding thousands of isoforms with different properties of interaction with post-synaptic molecules f…
Open article record in new tab ↗Dopamine D2 receptor (D2R)-mediated signalling is involved in reward, motivation and alcohol use disorder. Perturbation of the D2R system may influence an individual's response to alcohol. Alternative splicing of the D2R gene generates two isoforms: D2 long form (D2L) and D2 short form (D2S). It is unclear whether differences in the expression of D2L and D2S influence alcohol's effects. Here we examined if altered…
Abnormal accumulation of misfolded and hyperphosphorylated tau protein in brain is the defining feature of several neurodegenerative diseases called tauopathies, including Alzheimer's disease (AD). In AD, this pathological change is reflected by highly specific cerebrospinal fluid (CSF) tau biomarkers, including both phosphorylated and non-phosphorylated variants. Interestingly, despite tau pathology being at the…
Astrocytic tau aggregates are seen in several primary and secondary tauopathies, including progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and chronic traumatic encephalopathy (CTE). In all of these diseases, astrocytic tau consists mostly of the longer (4R) tau isoform, even when adjacent neuronal aggregates consist of a mixture of 3- and 4R tau, as in CTE. Even the rare astrocytic tau aggr…
Open article record in new tab ↗Arachidonylethanolamide (anandamide) acts as an endogenous ligand of cannabinoid receptors, while other N-acylethanolamines (NAEs), such as palmitylethanolamide and oleylethanolamide, show analgesic, anti-inflammatory, and appetite-suppressing effects through other receptors. In mammalian tissues, NAEs, including anandamide, are produced from glycerophospholipid via N-acyl-phosphatidylethanolamine (NAPE). The ɛ is…
Exchange proteins directly activated by cAMP (EPAC1 and EPAC2) are one of the several families of cellular effectors of the prototypical second messenger cAMP. To understand the origin and molecular evolution of EPAC proteins, we performed a comprehensive phylogenetic analysis of EPAC1 and EPAC2. Our study demonstrates that unlike its cousin PKA, EPAC proteins are only present in multicellular Metazoa. Within the…
Open article record in new tab ↗Crotoxin, from the venom of the South American rattlesnake Crotalus durissus terrificus, is a potent heterodimeric presynaptic β-neurotoxin that exists in individual snake venom as a mixture of isoforms of a basic phospholipase A2 (PLA2) subunit (CBa2, CBb, CBc, and CBd) and acidic subunit (CA1-4). Specific natural mutations in CB isoforms are implicated in functional differences between crotoxin isoforms. The thr…
Background Synaptic damage precedes neuron death in Alzheimer's disease (AD). Neurexins, NRXN1, NRXN2, and NRXN3, are presynaptic adhesion molecules that specify neuron synapses and regulate neurotransmitter release. Neurexins and postsynaptic neuroligins interact with amyloid beta oligomer (AβO) deposits in damaged synapses. NRXN3 gene variants have been associated with autism, addiction, and schizophrenia, howev…
Therapeutics aimed at blocking the cannabinoid 1 (CB1) receptor for treatment of obesity resulted in significant improvements in liver function, glucose uptake and pancreatic β-cell function independent of weight loss or CB1 receptor blockade in the brain, suggesting that peripherally-acting only CB1 receptor blockers may be useful therapeutic agents. Neuropsychiatric side effects and lack of tissue specificity pr…
Activation of G protein-coupled receptors results in multiple waves of signaling that are mediated by heterotrimeric G proteins and the scaffolding proteins β-arrestin 1/2. Ligands can elicit full or subsets of cellular responses, a concept defined as ligand bias or functional selectivity. However, our current understanding of β-arrestin-mediated signaling is still very limited. Here we provide a comprehensive vie…