Mechanistic Insights, Treatment Paradigms, and Clinical Progress in Neurological Disorders: Current and Future Prospects

Abstract

Neurodegenerative diseases (NDs) are a major cause of disability and are related to brain development. The neurological signs of brain lesions can vary from mild clinical shortfalls to more delicate and severe neurological/behavioral symptoms and learning disabilities, which are progressive. In this paper, we have tried to summarize a collective view of various NDs and their possible therapeutic outcomes. These diseases often occur as a consequence of the misfolding of proteins post-translation, as well as the dysfunctional trafficking of proteins. In the treatment of neurological disorders, a challenging hurdle to cross regarding drug delivery is the blood-brain barrier (BBB). The BBB plays a unique role in maintaining the homeostasis of the central nervous system (CNS) by exchanging components between the circulations and shielding the brain from neurotoxic pathogens and detrimental compounds. Here, we outline the current knowledge about BBB deterioration in the evolving brain, its origin, and therapeutic interventions. Additionally, we summarize the physiological scenarios of the BBB and its role in various cerebrovascular diseases. Overall, this information provides a detailed account of BBB functioning and the development of relevant treatments for neurological disorders. This paper will definitely help readers working in the field of neurological scientific communities.

Keywords: Alzheimer’s disease; Parkinson’s disease; blood–brain barrier; central nervous system; neurodegenerative diseases; oxidative stress.

Figure 1

(A) A three-dimensional view of the BBB anatomy, composed of vascular endothelial cells, vascular smooth machine cells, pericytes, microglia cells, astrocytes, and various neurons (Source: https://commons.wikimedia.org/wiki/File:Blood_vessels_brain_english.jpg, accessed on 18 December 2022); (B) the appearance of different neurodegenerative diseases, such as AD, and PD, ischemic and hemorrhagic stroke, and meningitis-associated damage due to the dysfunction of the BBB. This published work is licensed under a Creative Commons Attribution 3.0.

Figure 2

Schematic representation showing the various modes of transport system across the BBB includes carrier-mediated transport (CMT), receptor-mediated transport (RMT), efflux transporters, and ion transport, which are mainly governed by specialized endothelial cells of the BBB. Permission has been taken from the author and this work is licensed under a Creative Commons Attribution 4.0 International License Copyright © 2022. All rights reserved [68].

Figure 3

Replotting of a neurodegeneration pathway involved in AD pathogenesis, mediated by elevated levels of Aβ production, can independently and/or synergistically lead to the formation of filamentous Tau pathology [105].

Figure 4

Pathogenesis of PD—a variety of cellular mechanisms, with a background of oxidative stress, coupled with aging, lifestyle/environmental, and genetic factors, contribute to PD-related neurodegeneration. Permission was taken from the original authors for using this diagram [120] and licensed under a BMJ Publishing Group Ltd. and Copyright Clearance Center 2020.

Figure 5

A schematic illustration of muscle dysfunction and ALS pathology. The left panel depicts muscle tissue supplied by a normal nerve cell and the right panel shows the diseased state.

Figure 6

Illustration of the non-cell autonomously based pathogenesis of ALS. This published work is licensed under a Creative Commons Attribution 4.0 International License Copyright © 2021 and permission taken from the original authors for its re-use. All rights reserved [134].