No abstract

The imbalance between glutamate and γ‐aminobutyric acid (GABA) results in the loss of synaptic strength leading to neurodegeneration. The dogma on the field considered neurons as the main players in this excitation‐inhibition (E/I) balance. However, current strategies focusing only on neurons have failed to completely understand this condition, bringing up the importance of glia as an alternative modulator for neuroinflammation as glia alter the activity of neurons and is a source of both neurotrophic and neurotoxic factors. This review's primary goal is to illustrate the role of glia over E/I balance in the central nervous system and its interaction with neurons. Rather than focusing only on the neuronal targets, we take a deeper look at glial receptors and proteins that could also be explored as drug targets, as they are early responders to neurotoxic insults. This review summarizes the neuron–glia interaction concerning GABA and glutamate, possible targets, and its involvement in the E/I imbalance in neurodegenerative diseases like Alzheimer's disease, Parkinson's disease, Huntington's disease, and multiple sclerosis.

: Despite the advent of novel therapies which manage and control diabetes well, the increased risk of morbidity and mortality in diabetic subjects is associated with the devastating secondary complications it produces. Long-standing diabetes majorly drives the cellular and molecular alterations which eventually damage both small and large blood vessels. The complications are prevalent both in type I and type II diabetic subjects. The microvascular complications include diabetic neuropathy, diabetic nephropathy, diabetic retinopathy, while the macrovascular complications include diabetic heart disease and stroke. The current therapeutic strategy alleviates the complications to some extent but do not cure or prevent them perse, also the recent clinical trial outcomes in this field is disappointing. Success in the drug discovery of diabetic complications may be achieved by a better understanding of the underlying pathophysiology and in recognising the crucial factors contributing to the development and progression of the disease. In this review, we discuss the well-studied cellular mechanisms leading to the development and progression of diabetic complications. In addition, we also highlight the various therapeutic paradigms currently in clinical practice.

No abstract

Blood-Brain Barrier (BBB) acts as a highly impermeable barrier, presenting an impediment for the crossing of most classical drugs targeted for neurodegenerative diseases including Parkinson's disease (PD). Pertaining to the nature of drugs and other potential molecules, they impose unavoidable dose-restricted limitations eventually leading to the failure of therapy. However, many advancements in formulation technology and maneuvering of delivery approaches have been successful in delivering the drug to the brain in the therapeutic window. The nose to the brain (N2B) drug delivery employing the nano formulation, is one such emerging delivery approach, curbing both classical drug formulation and delivery-associated limitation. Later offers increased bioavailability, greater patient acceptance, less biological interference, circumvention of BBB, ample drug loading along with the controlled release of the drugs. In N2B delivery, the intranasal (IN) route carries therapeutics firstly into the nasal cavity followed by the brain through olfactory & trigeminal nerve connections linked with nasal mucosa. The N2B delivery approach is being explored for delivering other biologicals like neuropeptides and mitochondria. Meanwhile, this N2B delivery system is associated with vital challenges consisting of mucociliary clearance, degradation by enzymes, drug translocations by efflux mechanisms. These challenges finally culminated in the development of suitable surface-modified nano-carriers and ultrasound-assisted IN as FUS-IN technique which really has expanded the horizons of N2B drug delivery. Hence, nanotechnology, in collaboration with advances in the IN route of drug administration, has diversified a new marvel for treating PD. The present review discusses physiology, limitation of IN delivery along with current advances in nano carrier and technical development assisting N2B drug delivery.