Alzheimer's disease (AD) is a common age-related neurodegenerative disease characterized by progressive cognitive decline and irreversible memory impairment. Currently, several studies have failed to fully elucidate AD's cellular and molecular mechanisms. For this purpose, research on related cellular models may propose potential predictive models for the drug development of AD. Therefore, many cells characterized by neuronal properties are widely used to mimic the pathological process of AD, such as PC12, SH-SY5Y, and N2a, especially the PC12 pheochromocytoma cell line. Thus, this review covers the most systematic essay that used PC12 cells to study AD. We depict the cellular source, culture condition, differentiation methods, transfection methods, drugs inducing AD, general approaches (evaluation methods and metrics), and in vitro cellular models used in parallel with PC12 cells.

Alzheimer’s disease (AD) is a degenerative disease of the nervous system. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), a drug used to treat type 2 diabetes, have been shown to have neuroprotective effects. This systematic review and meta-analysis evaluated the effects and potential mechanisms of GLP-1 RAs in AD animal models. 26 studies were included by searching relevant studies from seven databases according to a predefined search strategy and inclusion criteria. Methodological quality was assessed using SYRCLE’s risk of bias tool, and statistical analysis was performed using ReviewManger 5.3. The results showed that, in terms of behavioral tests, GLP-1 RAs could improve the learning and memory abilities of AD rodents; in terms of pathology, GLP-1 RAs could reduce Aβ deposition and phosphorylated tau levels in the brains of AD rodents. The therapeutic potential of GLP-1 RAs in AD involves a range of mechanisms that work synergistically to enhance the alleviation of various pathological manifestations associated with the condition. A total of five clinical trials were retrieved fromClinicalTrials.gov. More large-scale and high-quality preclinical trials should be conducted to more accurately assess the therapeutic effects of GLP-1 RAs on AD.

As a subclass of the biopharmaceutical classification system (BCS) class II, basic drugs (BCS IIB) exhibit pH-dependent solubility and tend to generate supersaturation in the gastrointestinal tract, leading to less qualified in vitro–in vivo correlation (IVIVC). This study aims to develop a physiologically based multi-cup dissolution approach to improve the evaluation of the supersaturation for a higher quality of IVIVC and preliminarily explores the molecular mechanism of supersaturation and precipitation of ketoconazole affected by Polyvinylpyrrolidone–vinyl acetate copolymer (PVPVA) and hydroxypropyl methyl-cellulose (HPMC). The concentration of ketoconazole in each cup of the dynamic gastrointestinal model (DGIM) was measured using fiber optical probes. Molecular interactions between ketoconazole and PVPVA or HPMC were simulated by Materials Studio. The results demonstrated that PVPVA and HPMC improved and maintained the supersaturation of ketoconazole. PVPVA exhibited superior precipitation inhibitory effect on ketoconazole molecule aggregation due to slightly stronger van der Waals forces as well as unique electrostatic forces, thereby further enhancing in vitro drug absorption, which correlated well with in vivo drug absorption. Compared with a conventional dissolution apparatus paddle method, the DGIM improved the mean prediction error through the IVIVC from 19.30% to 9.96%, reaching the qualification criteria. In conclusion, the physiologically based multi-cup dissolution approach enables improved evaluation of supersaturation in gastrointestinal transportation of BCS IIB drug ketoconazole, enabling screening screen precipitation inhibitors and achieving qualified IVIVC for drug formulation studies.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) were initially approved for type 2 diabetes mellitus. Recent evidence suggests their therapeutic potential in various diseases, though their efficacy and safety remain incompletely understood. Here, we conduct an umbrella review including 123 meta-analyses covering 464 outcomes from 5617 articles to comprehensively assess the effectiveness and adverse events (AEs) of GLP-1 RAs across diverse outcomes. GLP-1 RAs showed trends toward improvements in endocrine and metabolic, cardiovascular, renal, and respiratory outcomes, cognitive function, with a potential reduction in fracture risk and all-cause mortality in certain populations. However, increased risks of certain AEs, including diabetic retinopathy, ketoacidosis, gastrointestinal events, and treatment discontinuation, were also observed. AMSTAR 2 assessments indicate that the existing evidence is limited by methodological shortcomings, including incomplete reporting of excluded studies, suboptimal literature search strategies, and insufficient evaluation of how bias in primary studies may influence meta-analytic estimates. Some outcomes did not reach statistical significance in all populations, highlighting the need for further high-quality clinical research. Careful consideration of potential benefits and risks is essential for optimizing treatment outcomes and ensuring patient safety when using GLP-1 RAs in clinical practice.