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), a neurodegenerative disorder that can occur in middle or old age, is characterized by memory loss, a continuous decline in thinking, behavioral and social skills that affect the ability of an individual to function independently. It is divided into sporadic and familial subtypes. Early-onset familial AD (FAD) is linked to mutations in genes coding for the amyloid-β protein precursor (AβPP), presenilin 1 (PS1), and presenilin 2 (PS2), which lead to alterations in AβPP processing, generation of the Amyloid-β peptide and hyperphosphorylation of tau protein. Identification of early biomarkers for AD diagnosis represents a challenge, and it has been suggested that molecular changes in neurodegenerative pathways identified in the brain of AD patients can be detected in peripheral non-neural cells derived from familial or sporadic AD patients. In the present study, we determined the protein expression, the proteomic and in silico characterization of skin fibroblasts from FAD patients with PS1 mutations (M146L or A246E) or from healthy individuals. Our results shown that fibroblasts from AD patients had increased expression of the autophagy markers LC3II, LAMP2 and Cathepsin D, a significant increase in total GSK3, phosphorylated ERK1/2 (Thr202/Tyr204) and phosphorylated tau (Thr231, Ser396, and Ser404), but no difference in the phosphorylation of Akt (Ser473) or the α (Ser21) and β (Ser9) GSK3 isoforms, highlighting the relevant role of abnormal protein post-translational modifications in age-related neurodegenerative diseases, such as AD. Both 2-DE gels and mass spectrometry showed significant differences in the expression of the signaling pathways associated with protein folding and the autophagic pathway mediated by chaperones with the expression of HSPA5, HSPE1, HSPD1, HSP90AA1, and HSPE1 and reticular stress in the FAD samples. Furthermore, expression of the heat shock proteins HSP90 and HSP70 was significantly higher in the cells from AD patients as confirmed by Western blot. Taken together our results indicate that fibroblasts from patients with FAD-PS1 present alterations in signaling pathways related to cellular stress, autophagy, lysosomes, and tau phosphorylation. Fibroblasts can therefore be useful in modeling pathways related to neurodegeneration, as well as for the identification of early AD biomarkers.

Alzheimer's disease is a neurodegenerative disorder whose etiology continues to be discussed, to the point that there are different hypotheses that seek to clarify it, in addition to the fact that, given its multifactorial nature, there are different risk factors associated with its development. As regards diagnosis, advances in molecule detection techniques at femtomolar scales have allowed to distinguish between healthy and diseased subjects at relatively early stages, although there is still much to be done. Aducanumab is a monoclonal antibody targeted against Ab, whose marketing approval by the Food and Drug Administration has been questioned by the international medical community, given the controversial results in clinical trials. Approval of this antibody as a disease-modifying treatment for Alzheimer's disease opens the door to continue using this type of treatments, but with different therapeutic targets, such as, for example, tau protein. Finally, given the population tendency towards longevity, conditions such as Alzheimer's disease are gaining epidemiological importance, which is why it is imperative to analyze and link what is being done in the social, familiar, clinical and research fields and, most importantly, to find those areas of opportunity for the benefit of the patient.

Background Alzheimer’s disease (AD) is a neurodegenerative disorder and the most common cause of dementia in the elderly. AD is characterized by short‐term to long‐term memory loss, confusion, mood changes, and language difficulties. Numerous studies have focused on the dysregulated genes in AD, but the pathogenesis is still unknown. The underlying risk factors remain largely unclear. The discovery of more accurate AD biomarkers will allow early detection and development of new treatments. Recently bioinformatics has become a relevant research tool for biomedicine. In this study, we explored differential expressed genes (DEGs) potentially involved in the pathogenesis of AD. Method Open access databases of RNA microarrays of tissue from brain and peripheral blood of AD patient, were analyzed after background correction and data normalization; Limma package was used for Differential expression Analysis (DEA) throw statistical R programming language. Data were corrected with the Benjamini and Hochberg approach, and the genes with p values equal to or less than 0.05 were considered significant. The direction of change in gene expression was determined by its variation in the “log2‐fold change” between controls and patients. We performed a functional enrichment analysis of GO using goana and topGO‐Limma. Result With the Brain tissue database, we obtained 17 down regulated genes (DR) and 81 up regulated genes (UR). Functional enrichment analysis of DEGs showed UR pathways: behavior, nervous systems process, post synapses, enzyme binding, while DR were: cellular component organization, RNA metabolic process, protein‐containing complex, nucleoside triphosphatase activity and RNA binding. The blood tissue database showed 850 genes DR and 693 genes UR. The functional enrichment analysis of these DEGs showed UR pathways: regulation of transcription by RNA polymerase‐II and RNA processing, while DR were: cell development and synapses. Finally, the intersection of the DEGs in the two databases showed 3 genes shared between the brain and blood. Conclusion Our in‐silico analysis of brain and blood databases identified several UR and DR genes; the detection of these genes could provide new insight into potential therapies for AD. However, more research is needed to validate these potential new biomarkers and correlate them with the clinical data at different AD stages.

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Since it was discovered, ischemic preconditioning (IPC) has motivated research groups around the world to develop preconditioning protocols capable of protecting tissues against prolonged insults. In 31 years of study, promising results have been obtained on the beneficial role of the CPI and the mechanisms involved in its regulation. Also, different preconditioning protocols that have obtained results similar to the classic CPI have been developed, among which is the exercise-induced preconditioning (EP), that has been proven to protect the heart against an insult, mitigate the atrophy of the heart muscle and increase physical performance in athletes and/or athletes.

Background Alzheimer's disease (AD) is a neurodegenerative disorder characterized by memory loss, neuronal degeneration and synaptic dysfunction, resulting in atrophy of the affected regions. The identification of early biomarkers for AD diagnosis has been a challenge due to the high individual variability in markers expression, thus the use of peripheral cells other than neuronal cells such as bone marrow or dental pulp mesenchymal cells, blood cells and fibroblasts represents an opportunity for the detection of early pathological changes of Alzheimer's disease patients. Moreover, neuronal cells differentiated from reprogram somatic cells, recapitulate brain cell pathological associated changes. Method We study the proteome using 2D‐PAGE and protein identification by mass spectrometry. Skin fibroblasts were cultured from patients with a mutation in Presenilin‐1 (A246E or M146L) and from control individuals of the Coriell Institute cell repository in Earl MEM salts medium with 15% non‐inactivated Fetal Bovine Serum. Fibroblast phenotype was confirmed by immunodetection of vimentin and S100A4 markers. We use Western Blot and qPCR techniques to evaluate changes in the expression of genes and proteins of particular pathways involved in the neurodegeneration of AD. Result Differences in protein expression in fibroblasts were identified between affected individuals and controls, related to cell adhesion, cytoskeleton, energy and glucose metabolism, ubiquitin‐proteasome pathway, autophagy and signal transduction, which have been previously found affected in neurons from AD patients. Conclusion Our results indicate that samples derived from fibroblasts from AD patients have a unique protein profile with respect to controls, both at expression level and proteins patterns, showing that peripheral cells can be useful in modeling degenerative pathways and biomarker identification for Alzheimer's disease.