Autophagy is a highly conserved lysosomal degradation pathway active at basal levels in all cells. However, under stress conditions, such as a lack of nutrients or trophic factors, it works as a survival mechanism that allows the generation of metabolic precursors for the proper functioning of the cells until the nutrients are available. Neurons, as post-mitotic cells, depend largely on autophagy to maintain cell homeostasis to get rid of damaged and/or old organelles and misfolded or aggregated proteins. Therefore, the dysfunction of this process contributes to the pathologies of many human diseases. Furthermore, autophagy is highly active during differentiation and development. In this review, we describe the current knowledge of the different pathways, molecular mechanisms, factors that induce it, and the regulation of mammalian autophagy. We also discuss its relevant role in development and disease. Finally, here we summarize several investigations demonstrating that autophagic abnormalities have been considered the underlying reasons for many human diseases, including liver disease, cardiovascular, cerebrovascular diseases, neurodegenerative diseases, neoplastic diseases, cancers, and, more recently, infectious diseases, such as SARS-CoV-2 caused COVID-19 disease.

Alzheimer’s disease (AD) is neurodegeneration that accounts for 60–70% of dementia cases. Symptoms begin with mild memory difficulties and evolve towards cognitive impairment. The underlying risk factors remain primarily unclear for this heterogeneous disorder. Bioinformatics is a relevant research tool that allows for identifying several pathways related to AD. Open-access databases of RNA microarrays from the peripheral blood and brain of AD patients were analyzed after background correction and data normalization; the Limma package was used for differential expression analysis (DEA) through statistical R programming language. Data were corrected with the Benjamini and Hochberg approach, and genes with p-values equal to or less than 0.05 were considered to be significant. The direction of the change in gene expression was determined by its variation in the log2-fold change between healthy controls and patients. We performed the functional enrichment analysis of GO using goana and topGO-Limma. The functional enrichment analysis of DEGs showed upregulated (UR) pathways: behavior, nervous systems process, postsynapses, enzyme binding; downregulated (DR) were cellular component organization, RNA metabolic process, and signal transduction. Lastly, the intersection of DEGs in the three databases showed eight shared genes between brain and blood, with potential use as AD biomarkers for blood tests.

Landau-Kleffner syndrome is a developmental epileptic encephalopathy that manifests mainly in pediatric patients, characterized by verbal auditory agnosia and focal, bilateral, and focal and diffuse epileptic activity, visualized through electroencephalographic recordings performed during sleep. It is a rare syndrome with a variable, multifactorial presentation and unknown etiology, although it has a genetic component in some cases. It is often associated with variants of the glutamate ionotropic receptor N-methyl-D-aspartate (NMDA) type subunit 2A (GRIN2A) gene, which encodes an NMDA receptor subunit of the same name that is involved in various neurophysiological processes. Modifications to this receptor could be associated with the clinical manifestations observed in patients. This review proposes a pathophysiological mechanism related to one of the clinical presentations of this disease, using information published in recent years, and contributes to the understanding of its pathology and the improvement of its management. This syndrome is a rare and complex disease; both its diagnosis and treatment are challenging, limiting patients’ therapeutic options and compromising their quality of life.

Dental pulp stem cells (DPSCs), mesenchymal stem cells found in deciduous and permanent teeth, possess multilineage differentiation potential, including neuronal commitment. Their ability to differentiate into neuronal phenotypes holds promise for neurodegenerative disease therapies, cell-based treatments, and tissue engineering. This study investigated the neuronal differentiation potential of DPSCs isolated from the first molar of a healthy 46-year-old female donor. Cells were cultured in a chemically defined medium (ITS 1%: Insulin, Transferrin, Selenium) with or without growth factors (BDNF, GDNF). Phenotypic characterization was performed via Western blot, immunofluorescence, RT-PCR, and flow cytometry. Undifferentiated DPSCs expressed mesenchymal (CD105, CD90, CD73, CD13) and neural/stem cell markers (βIII-tubulin, GFAP, Nestin, SOX2, Oct3/4, NANOG) but lacked hematopoietic markers (CD45, CD34, CD31, CD14). After 15 to 35 days in vitro (DIV) in ITS medium plus GDNF, DPSCs exhibited upregulated mature neuronal markers (NeuN, NF-M) and downregulated mesenchymal markers, confirming neuronal commitment. Electrophysiological analysis (whole-cell patch-clamp) revealed more hyperpolarized resting membrane potentials (RMP) in GDNF-treated cells (15 DIV) compared to controls (DMEM/F12 + 10% FBS), alongside increased membrane capacitance (Cm) and input resistance (Rin), suggesting progressive neuronal maturation. While action potentials were not observed, these electrophysiological shifts indicate early functional differentiation. In conclusion, prolonged GDNF exposure (15–35 DIV) in a chemically defined medium promoted DPSCs differentiation into a mature neuronal phenotype, marked indicated by NeuN expression and altered membrane properties. These findings highlight DPSCs as a viable tool for regenerative medicine and neurodegenerative disease research.