No abstract

: Deposits of amyloid β‐peptide (Aβ), reduced glucose uptake into brain cells, oxidative damage to cellular proteins and lipids, and excitotoxic mechanisms have all been suggested to play roles in the neurodegenerative process in Alzheimer's disease. Synapse loss is closely correlated with cognitive impairments in Alzheimer's disease, suggesting that the synapse may be the site at which degenerative mechanisms are initiated and propagated. We report that Aβ causes oxyradical‐mediated impairment of glucose transport, glutamate transport, and mitochondrial function in rat neocortical synaptosomes. Aβ induced membrane lipid peroxidation in synaptosomes that occurred within 1 h of exposure; significant decreases in glucose transport occurred within 1 h of exposure to Aβ and decreased further with time. The lipid peroxidation product 4‐hydroxynonenal conjugated to synaptosomal proteins and impaired glucose transport; several antioxidants prevented Aβ‐induced impairment of glucose transport, indicating that lipid peroxidation was causally linked to this adverse action of Aβ. FeSO4 (an initiator of lipid peroxidation), Aβ, and 4‐hydroxynonenal each induced accumulation of mitochondrial reactive oxygen species, caused concentration‐dependent decreases in 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide reduction, and reduced cellular ATP levels significantly. Aβ also impaired glutamate transport, an effect blocked by antioxidants. These data suggest that Aβ induces membrane lipid peroxidation, which results in impairment of the function of membrane glucose and glutamate transporters, altered mitochondrial function, and a deficit in ATP levels; 4‐hydroxynonenal appears to be a mediator of these actions of Aβ. These data suggest that oxidative stress occurring at synapses may contribute to the reduced glucose uptake and synaptic degeneration that occurs in Alzheimer's disease patients. They further suggest a sequence of events whereby oxidative stress promotes excitotoxic synaptic degeneration and neuronal cell death in a variety of different neurodegenerative disorders.

The cutaneous manifestations of COVID-19 patients have been increasingly reported, but not summarized, and the potential mechanisms remain to be investigated. Herein, we performed a comprehensive review of literatures (from inception to 30 May 2020) using PubMed, CNKI, medRxiv and bioRxiv with the terms "((novel coronavirus) OR (2019 novel coronavirus) OR (2019-nCoV) OR (Coronavirus disease 2019) OR (COVID-19) OR (SARS-CoV-2)) AND ((Dermatology) OR (skin) OR (rash) OR (cutaneous))" and "((ACE2) OR (Angiotensin-converting enzyme)) AND ((skin) OR (epidermis) OR (dermis))." Totally, 44 articles met the inclusion criteria. A total of 507 patients with cutaneous manifestations were summarized, and 96.25% patients were from Europe. The average age of the patients was 49.03 (range: 5-91) with a female ratio of 60.44%. The skin lesions were polymorphic, and erythema, chilblain-like and urticarial lesions were most common, occurring on an average of 9.92 days (range: 1-30) after the onset of systemic symptoms. The receptor of SARS-CoV-2, ACE2, was found to be expressed on skin, mainly on keratinocytes. Our review systematically presented the clinical characteristics of 507 patients and showed that skin might be the potential target of the infection according to ACE2 expression. More work should be done to better understand the underlying pathogenesis.