This failure is thought to be at least partly due to the downregulation by α-synuclein of Ret, the common co-receptor of glial cell line-derived neurorophic factor and neurturin. Growth/differentiation factor 5 is a member of the bone morphogenetic protein family of neurotrophic factors, that signals through the Ret-independent canonical Smad signaling pathway. Here, we review the evidence for the neurotrophic potential of growth/differentiation factor 5 in in vitro and in vivo models of Parkinson’s disease. We discuss new work on growth/differentiation factor 5’s mechanisms of action, as well as data showing that viral delivery of growth/differentiation factor 5 to the substantia nigra is neuroprotective in the α-synuclein rat model of Parkinson’s disease. These data highlight the potential for growth/differentiation factor 5 as a disease-modifying therapy for Parkinson’s disease.The presenilin genes (PSEN1 and PSEN2) are mainly responsible for causing early-onset familial Alzheimer’s disease, harboring ~300 causative mutations, and representing ~90% of all mutations associated with a very aggressive disease form. Presenilin 1 is the catalytic core of the γ-secretase complex that conducts the intramembranous proteolytic excision of multiple transmembrane proteins like the amyloid precursor protein, Notch-1, N- and E-cadherin, LRP, Syndecan, Delta, Jagged, CD44, ErbB4, and Nectin1a. Presenilin 1 plays an essential role in neural progenitor maintenance, neurogenesis, neurite outgrowth, synaptic function, neuronal function, myelination, and plasticity. Therefore, an imbalance caused by mutations in presenilin 1/γ-secretase might cause aberrant signaling, synaptic dysfunction, memory impairment, and increased Aβ42/Aβ40 ratio, contributing to neurodegeneration during the initial stages of Alzheimer’s disease pathogenesis. This review focuses on the neuronal differentiation dysregulation mediated by PSEN1 mutations in Alzheimer’s disease. Furthermore, we emphasize the importance of Alzheimer’s disease-induced pluripotent stem cells models in analyzing PSEN1 mutations implication over the early stages of the Alzheimer’s disease pathogenesis throughout neuronal differentiation impairment.Dynamic protein-protein interactions are essential for proper cell functioning. Homo-interaction events-physical interactions between the same type of proteins-represent a pivotal subset of protein-protein interactions that are widely exploited in activating intracellular signaling pathways. Capacities of modulating protein-protein interactions with spatial and temporal resolution are greatly desired to decipher the dynamic nature of signal transduction mechanisms. The emerging optogenetic technology, based on genetically encoded light-sensitive proteins, provides promising opportunities to dissect the highly complex signaling networks with unmatched specificity and spatiotemporal precision. Here we review recent achievements in the development of optogenetic tools enabling light-inducible protein-protein homo-interactions and their applications in optical activation of signaling pathways.Mechanisms of homeostatic plasticity promote compensatory changes of cellular excitability in response to chronic changes in the network activity. This type of plasticity is essential for the maintenance of brain circuits and is involved in the regulation of neural regeneration and the progress of neurodegenerative disorders. One of the most studied homeostatic processes is synaptic scaling, where global synaptic adjustments take place to restore the neuronal firing rate to a physiological range by the modulation of synaptic receptors, neurotransmitters, and morphology. However, despite the comprehensive literature on the electrophysiological properties of homeostatic scaling, less is known about the structural adjustments that occur in the synapses and dendritic tree. selleck chemical In this study, we performed a meta-analysis of articles investigating the effects of chronic network excitation (synaptic downscaling) or inhibition (synaptic upscaling) on the dendritic spine density of neurons. Our results indicate that spine density is consistently reduced after protocols that induce synaptic scaling, independent of the intervention type. Then, we discuss the implication of our findings to the current knowledge on the morphological changes induced by homeostatic plasticity.Cognitive impairment caused by chemotherapy, referred to as “chemobrain,” is observed in approximately 70% of cancer survivors. However, it is not completely understood how chemotherapy induces cognitive dysfunction, and clinical treatment strategies for this problem are lacking. Metformin, used as a first-line treatment for type 2 diabetes mellitus, is reported to reduce the effects of chemobrain. Recently, several studies have examined the effect of metformin in rescuing chemobrain. This review discusses recent clinical/preclinical studies that addressed some mechanisms of chemobrain and evaluates the effect of metformin in rescuing chemobrain and its potential mechanisms of action.Taking advantage of the fast-growing knowledge of RNA-binding proteins (RBPs) we review the signature of downregulated genes for RBPs in the transcriptome of induced pluripotent stem cell neurons (iNeurons) modelling the neurodevelopmental Rubinstein Taybi Syndrome (RSTS) caused by mutations in the genes encoding CBP/p300 acetyltransferases. We discuss top and functionally connected downregulated genes sorted to “RNA processing” and “Ribonucleoprotein complex biogenesis” Gene Ontology clusters. The first set of downregulated RBPs includes members of hnRNHP (A1, A2B1, D, G, H2-H1, MAGOHB, PAPBC), core subunits of U small nuclear ribonucleoproteins and Serine-Arginine splicing regulators families, acting in precursor messenger RNA alternative splicing and processing. Consistent with literature findings on reduced transcript levels of serine/arginine repetitive matrix 4 (SRRM4) protein, the main regulator of the neural-specific microexons splicing program upon depletion of Ep300 and Crebbp in mouse neurons, RSTSin chromatin regulation, the impact of its defect on neurons’ post-transcriptional regulation of gene expression and the potential use of epidrugs in therapeutics of RBP-caused neurodevelopmental disorders.