Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0220723 (PCA)
 4,687 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Activation of macroautophagy/autophagy, a key mechanism involved in the degradation and removal of aggregated proteins, can successfully reverse Huntington disease phenotypes in various model systems. How neuronal autophagy impairments need to be considered in Huntington disease progression to achieve a therapeutic effect is currently not known. In this study, we used a mouse model of HTT (huntingtin) protein aggregation to investigate how different methods and timing of autophagy activation influence the efficacy of autophagy-activating treatment in vivo. We found that overexpression of human TFEB, a master regulator of autophagy, did not decrease mutant HTT aggregation. On the other hand, Becn1 overexpression, an autophagic regulator that plays a key role in autophagosome formation, partially cleared mutant HTT aggregates and restored neuronal pathology, but only when administered early in the disease progression. When Becn1 was administered at a later stage, when prominent mutant HTT accumulation and autophagy impairments have occurred, Becn1 overexpression did not rescue the mutant HTT-associated phenotypes. Together, these results demonstrate that the targets used to activate autophagy, as well as the timing of autophagy activation, are crucial for achieving efficient therapeutic effects.Abbreviations: AAV: adeno-associated viral vectors; ACTB: actin beta; BECN1: beclin 1, autophagy related; DAPI: 4',6-diamidino-2-phenylindole; GO: gene ontology; HD: Huntington disease; HTT: huntingtin; ICQ: Li's intensity correlation quotient; IHC: immunohistochemistry; LAMP1: lysosomal-associated membrane protein 1; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; mHTT: mutant huntingtin; PCA: principal component analysis; PPP1R1B/DARPP-32: protein phosphatase 1 regulatory inhibitor subunit 1B; SQSTM1: sequestosome 1; TFEB: transcription factor EB; WB: western blot; WT: wild-type.
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PMID:Impact of differential and time-dependent autophagy activation on therapeutic efficacy in a model of Huntington disease. 3237 3

Seborrheic dermatitis (SD) is a chronic, recurrent, inflammatory skin disorder occurring in areas rich in sebaceous glands. It manifests clinically as erythematous macules or plaques with varying levels of scaling and associated pruritus. Although the pathogenesis of SD has yet to be fully understood, Malassezia yeasts, hormones, sebum levels, and immune response are known to play important roles. Additional factors including drugs, winter temperatures, and stress may exacerbate SD. Current available treatments include antifungal agents, topical low-potency steroids, and calcineurin inhibitors. We aimed to evaluate the effectiveness of a topical non-steroidal cream in treating facial seborrheic dermatitis (FSD). We performed a case series of 11 patients with mild or moderate FSD and a history of several previous treatments without improvement. The patients were treated for 8 weeks with a topical non-steroidal facial cream (NSFC) containing zinc PCA, piroctone olamine, hydroxyphenyl propamidobenzoic acid, biosaccharide gum-2, and stearyl glycyrrhetinate. Signs and symptoms and tolerance were assessed before, during, and at the end of treatment. All of the patients had improved symptoms of FSD (desquamation, pruritus, erythema, and stinging sensation); 81.8% showed an excellent response and 18.1% showed a good response. None of the patients had adverse effects. J Drugs Dermatol. 2020;19(6): doi:10.36849/JDD.2020.5121.
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PMID:Non-Steroidal Topical Therapy for Facial Seborrheic Dermatitis. 3257 15