Journal of Translational Neurosciences

Description

Globally, Alzheimer's disease (AD) is the leading cause of dementia. Patients and those who care for them must concentrate on symptom management because there is no known treatment for Alzheimer's disease. In terms of synaptic function, the blood-brain barrier, and neurovascular coupling, it is now known that astrocytes and microglia play distinct physiological roles. Because current medications are intended to alleviate Alzheimer's disease symptoms, the search for medications that can halt the degenerative process in dementia sufferers continues. Potential treatments for neuroinflammatory diseases include medications that target pathological changes without interfering with the normal function of glia, like getting rid of amyloid-beta deposits. Neuron-astrocyte-microglia interactions are so complex that developing AD medications that are both effective and preventative will require new approaches and strategic targets. Donepezil, choline alphoscerate, galantamine, dextromethorphan, palmitoylethanolamide, citalopram, resveratrol, and solanezumab are among the AD-treating medications that were the focus of this review. Neurodegenerative conditions like Alzheimer's disease (AD) are characterized by chronic inflammation in the Central Nervous System (CNS). The Blood-Brain Barrier (BBB) or blood-spinal cord barrier (BSCB) is the third anatomical barrier that divides the central nervous system (CNS). The arachnoid barrier and the blood-cerebrospinal fluid barrier at the Choroid Plexus (CP).

Fundamental Principal Components of the CNS

Contrasts in the structures of the BBB and BSCB, as well as variations in the cranial and spinal meninges, white matter, and grey matter, may directly correlate with the susceptibility of various anatomical regions of the body to neuroinflammatory events. Multiple sclerosis (MS), Parkinson's disease (PD), Alzheimer's disease (AD), stroke, epilepsy, and Traumatic Brain Injury (TBI) are known to have a predisposition to the aforementioned barriers. This predisposition is linked to activate endothelial cells that exhibit a altered phenotype and a decrease in the number of tight junction proteins. The etiology of neurodegeneration is different, and proof proposes that extraneous factors, for example, way of life and compound openings are associated with the improvement of these problems. In the current field of brain research, it would be necessary to investigate the connections between neurons and glia. Numerous types of research on dementia and aging now focus on glia rather than nerve cells. In particular, it is now understood that astrocytes and microglia, which were previously thought to only assist neurons, perform distinct physiological functions in synapse function, the blood-brain barrier, and neurovascular coupling. Neurons and glia's dysfunctional or abnormal interaction can upset the normal balance of brain physiology. Microglia play a crucial role in the normal functioning of the neuron-glia triad, which is essential for the proper organization of the brain, despite the fact that neurons are thought to be the fundamental principal components of the CNS. Astrocytes are the mass multitudinous subtypes of glial cells inside the focal sensory system. Glial Fibrillary Acidic Protein (GFAP), which is responsible for the formation of intermediate filaments, enhances astrocytes' cell bodies as well as their essential processes. Cholinergic activity in the hippocampus of the brain regulates neuronal and network activity, as well as synaptic transmission and plasticity. Numerous distinct brain functions depend on this system.

Primary Source of Cholinergic Innervation to the Cortex

 According to a report, in vivo and in vitro studies have shown that muscarinic acetylcholine receptors (mAChRs) regulate both Ca2+ boosting in astrocytes and hippocampal Long-Term Potentiation (LTP), a cellular component of learning and memory that is elicited by cholinergic action. During the following actions, astrocytic Ca2+ activity rises: the activation of the locus coeruleus, sensory stimulation, or the pharmacological strengthening of the neural task. In addition, it has been demonstrated that the above actions, which increase astrocytic Ca2+ through mAChRs, can activate the nucleus basalis of meynert (NBM), the primary source of cholinergic innervation to the cortex. Because neuronal cholinergic signaling is thought to be anti-inflammatory and anti-oxidative, cholinergic drugs that directly or indirectly target cholinergic glial interactions could be used to treat neurodegenerative conditions like Alzheimer's disease by controlling neuroinflammation and oxidative stress. The drugs were evaluated based on their pharmacokinetic characteristics, underlying mechanisms, dose, clinical effects, and documented pathologies, as determined by previous experimental and clinical research. The treatment for Alzheimer's disease that is currently available aims to minimize its symptoms. Consequently, it is still essential to look for medications that can slow the degenerative process in dementia patients. After 48 weeks of treatment, donepezil can lower blood levels of amyloid-beta (A), lower total tau protein expression, and improve cognitive function by reducing hippocampus atrophy. Galantamine and donepezil had no effect on the proliferation of astrocytes.