Cdk5-mediated oligodendrocyte myelin breakdown and neuroinflammation: Implications for the link between Type 2 Diabetes and Alzheimer's disease.

Oligodendrocytes, crucial myelinating glia in the central nervous system, play a vital role in maintaining axonal integrity and facilitating efficient nerve impulse conduction. The degradation of myelin in oligodendrocytes has been implicated in Alzheimer's disease (AD) and cognitive dysfunction. Interestingly, individuals with Type 2 Diabetes (T2D) have a significantly higher likelihood of developing cognitive impairment, possibly due to insulin resistance and glucose toxicity within the central nervous system (CNS). However, the precise relationship between these two disorders remains elusive. Our study proposes a potential link between T2D and AD, involving Cdk5-mediated breakdown of oligodendrocyte myelin and neuroinflammation. In the context of T2D, glucose toxicity in oligodendrocytes leads to heightened Cdk5 kinase activity and cPLA2 hyperactivation, resulting in chronic inflammation and myelin deterioration. This myelin breakdown in oligodendrocytes is thought to contribute to the development of AD and cognitive dysfunction. Notably, the administration of a Cdk5 inhibitor (TFP5) effectively alleviates neuroinflammation and myelin degradation. Moreover, our findings demonstrate heightened activity of Cdk5, cPLA2, and phospho-cPLA2 levels in the brain of a mouse model with Type 2 Diabetes (T2D). Hence, our findings suggest that targeting Cdk5 could be a promising therapeutic strategy to counteract AD pathogenesis in T2D-related conditions.

Disentangling potential genotypes for macro and micro nutrients and polymorphic markers in Chickpea.

The present investigation was conducted to assess the nutritional diverseness and identify novel genetic resources to be utilized in chickpea breeding for macro and micro nutrients. The plants were grown in randomized block design. Nutritional and phytochemical properties of nine chickpea genotypes were estimated. The EST sequences from NCBI database were downloaded in FASTA format, clustered into contigs using CAP3, mined for novel SSRs using TROLL analysis and primer pairs were designed using Primer 3 software. Jaccard's similarity coefficients were used to compare the nutritional and molecular indexes followed by dendrograms construction employing UPGMA approach. The genotypes PUSA-1103, K-850, PUSA-1108, PUSA-1053 and the EST-SSR markers including the 5 newly designed namely ICCeM0012, ICCeM0049, ICCeM0067, ICCeM0070, ICCeM0078, SVP55, SVP95, SVP96, SVP146, and SVP217 were found as potential donor/marker resources for the macro-micro nutrients. The genotypes differed (p < 0.05) for nutritional properties. Amongst newly designed primers, 6 were found polymorphic with median PIC (0.46). The alleles per primer ranged 1 to 8. Cluster analysis based on nutritional and molecular diversities partially matched to each other in principle. The identified novel genetic resources may be used to widen the germplasm base, prepare maintainable catalogue and identify systematic blueprints for future chickpea breeding strategies targeting macro-micro nutrients.

Understanding the roles and regulation of mitochondrial microRNAs (MitomiRs) in neurodegenerative diseases: Current status and advances.

MicroRNAs (miRNA) are a class of small non-coding RNA, roughly 21-22 nucleotides in length, which are master gene regulators. These miRNAs bind to the mRNA's 3' - untranslated region and regulate post-transcriptional gene regulation, thereby influencing various physiological and cellular processes. Another class of miRNAs known as mitochondrial miRNA (MitomiRs) has been found to either originate from the mitochondrial genome or be translocated directly into the mitochondria. Although the role of nuclear DNA encoded miRNA in the progression of various neurological diseases such as Parkinson's disease, Alzheimer's disease, Huntington's disease, etc. is well known, accumulating evidence suggests the possible role of deregulated mitomiRs in the progression of various neurodegenerative diseases with unknown mechanism. We have attempted to outline the current state of mitomiRs role in controlling mitochondrial gene expression and function through this review, paying particular attention to their contribution to neurological processes, their etiology, and their potential therapeutic use.