Cell signaling associated with internalization of 67 kDa laminin receptor (67LR) by soluble laminin and its implication for protection against neurodegenerative diseases

Various isoforms of laminins are present in the basement membranes complexed with other structural proteins.In the central nervous system(CNS),they are primarily localized to the basement membranes of blood vessels and reactive astrocytes.Limited amounts of various laminin isoforms are also associated with neuronal cell bodies and axons,which are referred to as“neuronal”laminins(Yamamoto et al.,1988).They exist in a soluble form,free from other basement membrane proteins.Neurons either produce these soluble laminins or acquire them from astroglial cells.Laminin stimulates neuritogenesis and confers neuroprotection in vitro,but their exact role of these neuronal soluble laminins in the CNS is yet unknown.

Educational, psychosocial, and clinical impact of SARS-CoV-2 (COVID-19) pandemic on medical students in the United States

BACKGROUND The coronavirus disease 2019(COVID-19)pandemic altered education,exams,and residency applications for United States medical students.AIM To determine the specific impact of the pandemic on US medical students and its correlation to their anxiety levels.METHODS An 81-question survey was distributed via email,Facebook and social media groups using REDCapTM.To investigate risk factors associated with elevated anxiety level,we dichotomized the 1-10 anxiety score into low(≤5)and high(≥6).This cut point represents the 25th percentile.There were 90(29%)shown as low anxiety and 219(71%)as high anxiety.For descriptive analyses,we used contingency tables by anxiety categories for categorical measurements with chi square test,or mean±STD for continuous measurements followed by t-test or Wilcoxson rank sum test depending on data normality.Least Absolute Shrinkage and Selection Operator was used to select important predictors for the final multivariate model.Hierarchical Poisson regression model was used to fit the final multivariate model by considering the nested data structure of students clustered within State.RESULTS 397 medical students from 29 states were analyzed.Approximately half of respondents reported feeling depressed since the pandemic onset.62%of participants rated 7 or higher out of 10 when asked about anxiety levels.Stressors correlated with higher anxiety scores included“concern about being unable to complete exams or rotations if contracting COVID-19”(RR 1.34;95%CI:1.05-1.72,P=0.02)and the use of mental health services such as a“psychiatrist”(RR 1.18;95%CI:1.01-1.3,P=0.04).However,those students living in cities that limited restaurant operations to exclusively takeout or delivery as the only measure of implementing social distancing(RR 0.64;95%CI:0.49-0.82,P<0.01)and those who selected“does not apply”for financial assistance available if needed(RR 0.83;95%CI:0.66-0.98,P=0.03)were less likely to have a high anxiety.CONCLUSION COVID-19 significantly impacted medical students in numerous ways.Medical student education and clinical readiness were reduced,and anxiety levels increased.It is vital that medical students receive support as they become physicians.Further research should be conducted on training medical students in telemedicine to better prepare students in the future for pandemic planning and virtual healthcare.

Cyclic adenosine monophosphate-elevating agents inhibit amyloid-beta internalization and neurotoxicity:their action in Alzheimer's disease prevention

Recently,we have found that various intracellular cyclic adenosine monophosphate(cAMP)-e leva ting agents,both pharmacological(dibutyryl-cAMP,forskolin,and rolipram)and physiological(pituitary adenylate cyclase-activating polypeptide),decrease cell-surface levels of 67-kDa laminin receptor(67LR)and cellular prion protein(PrP~C).

Nogo-A receptor internalization by cyclic adenosine monophosphate in overcoming axonal growth inhibitors after stroke

Currently,there are no clinically proven drugs for recovery from stroke and other neuronal injuries such as traumatic brain injury and spinal cord injury.Recovery therapy requires axonal regeneration,which is inhibited by diverse axonal growth inhibitors,such as Nogo-A,myelin-associated glycoprotein(MAG),oligodendrocyte myelin glycoprotein(OMgp),and chondroitin sulfate proteoglycans(CSPGs)(Chaudhry and Filbin,2007;Carmichael,2010;Schwab and Strittmatter,2014).

Neuroprotection by resveratrol-glucuronide and quercetin-glucuronide via binding to polyphenol-and glycosaminoglycan-binding sites in the laminin receptor

The dietary polyphenolic compounds resveratrol and quercetin prevent neurodegenerative diseases in experimental models;however, they reach the brain only in nanomolar concentrations in the glucuronidated and sulfated forms, and not as the aglycone parent form(Pasinetti et al.,2015).