Prevention of Chronic Diabetic Neuropathy and Diabetes-Associated Cognitive Impairment Using Medicinal Herbs (Cassia Angustifolia and Nigella Sativa).

Nodal regions, areas of intensive contact between Schwann cells and axons, may be exceptionally vulnerable to diabetes-induced changes because they are exposed to and impacted by the metabolic implications of diabetes. Insulin receptors, glucose transporters, Na+ and K+ channels, and mitochondria are abundant in nodes, all of which have been linked to the development and progression of Diabetic Peripheral Neuropathy (DPN) and Type 1 Diabetes Mellitus (T1DM)-associated cognitive impairment. Our study aimed to evaluate if the administration of Nigella sativa (NS) and Cassia angustifolia (CA) prevented diabetes-associated nervous system deficits in hyperglycemic mice. We developed T1DM mice through Streptozotocin (STZ) injections and validated the elevations in blood glucose levels. NS and CA were administered immediately upon the induction of diabetes. Behavioral analysis, histopathological evaluations, and assessment of molecular biomarkers (NR2A, MPZ, NfL) were performed to assess neuropathy and cognitive impairment. Improvements in memory, myelin loss, and the expression of synaptic proteins, even with the retention of hyperglycemia, were evident in the mice who were given a dose of herbal products upon the detection of hyperglycemia. NS was more beneficial in preventing memory impairments, demyelination, and synaptic dysfunction. The findings indicate that including these herbs in the diets of diabetic as well as pre-diabetic patients can reduce complications associated with T1DM, notably diabetic peripheral neuropathy and cognitive deficits associated with T1DM.

Therapeutic Potential of Nitrogen-Doped Rutin-Bound Glucose Carbon Dots for Alzheimer's Disease.

The blood-brain barrier (BBB) prevents the use of many drugs for the treatment of neurological disorders. Recently, nitrogen-doped carbon dots (NCDs) have emerged as promising nanocarriers to cross BBB. The primary focus of our study was to evaluate the effectiveness of NCDs for the symptomatic treatment of Alzheimer's disease (AD). In this study, we developed and characterized NCDs bound to rutin, a flavonoid with known benefits for AD. Despite its benefits, the transportation of rutin via NCDs for AD therapy has not been explored previously. We characterized the particles using FTIR and UV-visible spectroscopy followed by atomic force microscopy. Once the design was optimized and validated, we performed in vivo testing via a hemolytic assay to optimize the dosage. Preliminary in vitro testing was performed in AlCl3-induced rat models of AD whereby a single dose of 10 mg/kg NCDs-rutin was administered intraperitoneally. Interestingly, this single dose of 10 mg/kg NCDs-rutin produced the same behavioral effects as 50 mg/kg rutin administered intraperitoneally for 1 month. Similarly, histological and biomarker profiles (SOD2 and TLR4) also presented significant protective effects of NCDs-rutin against neuronal loss, inflammation, and oxidative stress. Hence, NCDs-rutin are a promising approach for the treatment of neurological diseases.

The Role of Tau Proteoforms in Health and Disease.

Tau is a microtubule-associated binding protein in the nervous system that is known for its role in stabilizing microtubules throughout the nerve cell. It accumulates as ß-sheet-rich aggregates and neurofibrillary tangles, leading to an array of different pathologies. Six splice variants of this protein, generated from the microtubule-associated protein tau (MAPT) gene, are expressed in the brain. Amongst these variants, 0N3R, is prominent during fetal development, while the rest, 0N4R, 1N3R, 1N4R, 2N3R, and 2N4R, are expressed in postnatal stages. Tau isoforms play their role separately or in combination with others to contribute to one or multiple neurodegenerative disorders and clinical syndromes. For instance, in Alzheimer's disease and a subset of frontotemporal lobar degeneration (FTLD)-MAPT (i.e., R406W and V337M), both 3R and 4R isoforms are involved; therefore, they are called 3R/4R mix tauopathies. On the other hand, 4R isoforms are aggregated in progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and a majority of FTLD-MAPT and these diseases are called 4R tauopathies. Similarly, Pick's disease has an association with 3R tau isoforms and is thereby referred to as 3R tauopathy. Unlike 3R isoforms, the 4R variants have a faster rate of aggregation that accelerates the associated neurodegenerative mechanisms. Moreover, post-translational modifications of each isoform occur at a different rate and dictate their physiological and pathological attributes. The smallest tau isoform (0N3R) is highly phosphorylated in the fetal brain but does not lead to the generation of aggregates. On the other hand, proteoforms in the adult human brain undergo aggregation upon their phosphorylation and glycation. Expanding on this knowledge, this article aims to review the physiological and pathological roles of tau isoforms and their underlying mechanisms that result in neurological deficits. Physiological and pathological relevance of microtubule-associated protein tau (MAPT): Tau exists as six splice variants in the brain, each differing with respect to expression, post-translational modifications (PTMs), and aggregation kinetics. Physiologically, they are involved in the stabilization of microtubules that form the molecular highways for axonal transport. However, an imbalance in their expression and the associated PTMs leads to a disruption in their physiological function through the formation of neurofibrillary tangles that accumulate in various regions of the brain and contribute to several types of tauopathies.