Amyloid Precursor Protein: A Regulatory Hub in Alzheimer's Disease.

Decades of research have demonstrated an incontrovertible role of amyloid-ß (Aß) in the etiology of Alzheimer's disease (AD). However, the overemphasis on the pathological impacts of Aß may obscure the role of its metabolic precursor, amyloid precursor protein (APP), as a significant hub in the occurrence and progression of AD. The complicated enzymatic processing, ubiquitous receptor-like properties, and abundant expression of APP in the brain, as well as its close links with systemic metabolism, mitochondrial function and neuroinflammation, imply that APP plays multifaceted roles in AD. In this review, we briefly describe the evolutionarily conserved biological characteristics of APP, including its structure, functions and enzymatic processing. We also discuss the possible involvement of APP and its enzymatic metabolites in AD, both detrimental and beneficial. Finally, we describe pharmacological agents or genetic approaches with the capability to reduce APP expression or inhibit its cellular internalization, which can ameliorate multiple aspects of AD pathologies and halt disease progression. These approaches provide a basis for further drug development to combat this terrible disease.

Amyloid precursor protein facilitates SARS-CoV-2 virus entry into cells and enhances amyloid-ß-associated pathology in APP/PS1 mouse model of Alzheimer's disease.

Although there are indications of a trend towards less severe acute respiratory symptoms and a decline in overall lethality from the novel Coronavirus Disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), more and more attention has been paid to the long COVID, including the increased risk of Alzheimer's disease (AD) in COVID-19 patients. In this study, we aim to investigate the involvement of N-terminal amyloid precursor protein (APP) in SARS-CoV-2-induced amyloid-ß (Aß) pathology. Utilizing both in vitro and in vivo methodologies, we first investigated the interaction between the spike protein of SARS-CoV-2 and N-terminal APP via LSPR and CoIP assays. The in vitro impacts of APP overexpression on virus infection were further evaluated in HEK293T/ACE2 cells, SH-SY5Y cells, and Vero cells. We also analyzed the pseudovirus infection in vivo in a mouse model overexpressing human wild-type APP. Finally, we evaluated the impact of APP on pseudovirus infection within human brain organoids and assessed the chronic effects of pseudovirus infection on Aß levels. We reported here for the first time that APP, the precursor of the Aß of AD, interacts with the Spike protein of SARS-CoV-2. Moreover, both in vivo and in vitro data further indicated that APP promotes the cellular entry of the virus, and exacerbates Aß-associated pathology in the APP/PS1 mouse model of AD, which can be ameliorated by N-terminal APP blockage. Our findings provide experimental evidence to interpret APP-related mechanisms underlying AD-like neuropathology in COVID-19 patients and may pave the way to help inform risk management and therapeutic strategies against diseases accordingly.

Clinical treatment of lumbar disc herniation.

OBJECTIVE: To investigate the clinical effect of radiofrequency ozone and injection of anti-inflammatory analgesic solution into the internal orifice of nerve root combined with traditional Chinese medicine hook operation in the treatment of lumbar disc herniation. METHODS: Patients with lumbar disc herniation who were admitted to our hospital on December 20, 2017 and June 19, 2019 were selected as the main research objects, and the included patients were divided into control group, basic group and comprehensive group by random number table method. Control group was treated with radiofrequency ozone therapy, basic group was treated with injection of anti-inflammatory analgesic solution into the internal orifice of nerve root in addition to the control group, comprehensive group was treated with traditional Chinese medicine hook operation in addition to the basic group. The clinical treatment effects were observed. RESULTS: A total of 153 patients were included in this study, including 40 in the control group, 40 in the basic group, and 73 in the comprehensive group. The results showed that the NRS scores of control group were 3±0.98, 2±0.93 and 2±0.85 at 1 month, 3 months and 1 year after treatment, respectively. NRS scores in the basic group were 3±0.18, 2±0.33, and 2±0.15, respectively. NRS scores in the comprehensive group were 2±0.78, 1±0.54, and 1±0.77, respectively. Compared with the control group, there were significant differences in basic group and comprehensive group at each time point (P < 0. 05). At the same time, compared with the basic group, the NRS score of the comprehensive group was statistically different (P < 0.05). CONCLUSION: Radiofrequency ozone and injection of anti-inflammatory analgesic solution into the internal orifice of nerve root combined with hook operation can obtain good short-term and medium-term effects in the treatment of lumbar disc herniation. It is a safe and effective minimally invasive treatment method. KEY WORDS: Internal orifice of nerve root, Lumbar disc herniation, Ozone.