Depression is currently recognized as a crucial problem in everyday clinical practice, in light of ever-increasing rates of prevalence, as well as disability, morbidity, and mortality related to this disorder. Currently available antidepressant drugs are notoriously problematic, with suboptimal remission rates and troubling side-effect profiles. Their mechanisms of action focus on the monoamine hypothesis for depression, which centers on the disruption of serotonergic, noradrenergic, and dopaminergic neurotransmission in the brain. Nevertheless, views on the pathophysiology of depression have evolved notably, and the comprehension of depression as a complex neuroendocrine disorder with important systemic implications has sparked interest in a myriad of novel neuropsychopharmacological approaches. Innovative pharmacological targets beyond monoamines include glutamatergic and GABAergic neurotransmission, brain-derived neurotrophic factor, various endocrine axes, as well as several neurosteroids, neuropeptides, opioids, endocannabinoids and endovanilloids. This review summarizes current knowledge on these pharmacological targets and their potential utility in the clinical management of depression.

At present, Alzheimer’s disease (AD) and type 2 diabetes mellitus (T2DM) are two highly prevalent disorders worldwide, especially among elderly individuals. T2DM appears to be associated with cognitive dysfunction, with a higher risk of developing neurocognitive disorders, including AD. These diseases have been observed to share various pathophysiological mechanisms, including alterations in insulin signaling, defects in glucose transporters (GLUTs), and mitochondrial dysfunctions in the brain. Therefore, the aim of this review is to summarize the current knowledge regarding the molecular mechanisms implicated in the association of these pathologies as well as recent therapeutic alternatives. In this context, the hyperphosphorylation of tau and the formation of neurofibrillary tangles have been associated with the dysfunction of the phosphatidylinositol 3-kinase and mitogen-activated protein kinase pathways in the nervous tissues as well as the decrease in the expression of GLUT-1 and GLUT-3 in the different areas of the brain, increase in reactive oxygen species, and production of mitochondrial alterations that occur in T2DM. These findings have contributed to the implementation of overlapping pharmacological interventions based on the use of insulin and antidiabetic drugs, or, more recently, azeliragon, amylin, among others, which have shown possible beneficial effects in diabetic patients diagnosed with AD.

: Aging is a time-dependent inevitable process, in which cellular homeostasis is affected, which has an impact on tissue function. This represents a risk factor for the development of numerous non-transmissible diseases. In consequence, the scientific community continues to search for therapeutic measures capable of improving quality of life and delaying cellular aging. At the center of this research is metformin, a widely used drug in Type 2 Diabetes Mellitus treatment that has a reduced adverse effects profile. Furthermore, there is evidence that this drug has beneficial health effects that go beyond its anti-hyperglycemic properties. Among these effects, its geronto-protection capability stands out. There is growing evidence that points out to an increased life expectancy as well as quality of life in model organisms treated with metformin. Therefore, there is an abundance of research centered on elucidating the mechanism through which metformin has its anti-aging effects. Among these, the AMPK, mTORC1, SIRT1, FOXO, NF.kB, and DICER1 pathways can be mentioned. Furthermore, studies have highlighted the possibility of a role for gut microbiome in these processes. The next step is the design of clinical essays that have as a goal evaluating the efficacy and safety of metformin as an anti-aging drug in humans to create a paradigm in the medical horizon. The question being if metformin is in fact the new anti-aging therapy in humans?