Neurodegenerative disorders: Assessing the impact of natural vs drug-induced treatment options

Abstract

Neurodegenerative illnesses refer to the gradual, cumulative loss of neural activity. Neurological conditions are considered to be the second leading cause of mortality in the modern world and the two most prevalent ones are Parkinson's disease and Alzheimer's disease. The negative side effects of pharmaceutical use are a major global concern, despite the availability of many different treatments for therapy. We concentrated on different types of neurological problems and their influence on targets, in vitro, in vivo, and in silico methods toward neurological disorders, as well as the molecular approaches influencing the same, in the first half of the review. The bulk of the second half of the review focuses on the many categories of treatment possibilities, including natural and artificial. Nevertheless, herbal treatment solutions are piquing scholarly attention due to their anti-oxidative properties and accessibility. However, more quality investigations and innovations are undoubtedly needed to back up these conclusions.

Keywords: herbal; mechanistic approach; neurodegenerative disorders; synthetic; treatment.

FIGURE 1

Explains the role of tau and beta‐amyloid protein in ROS production. Tau not only causes a rapid increase in the generation of Ca2+ ions, which raises levels of reactive oxygen species, but it also oligomerizes to produce pores on the surfaces of astrocytes and lowers the activity of complex 1 located on the mitochondrial cell structure. The beta‐amyloid build‐up causes pores to develop, which also speeds up the generation of Ca2+ ions, however, it exercises its effect in three ways by firstly reducing the levels of GSH, secondly increasing the levels of PARP and thirdly on NAD(+) by decreasing its levels. Adapted from: Abramov et al. (2020). Created with BioRender.com.

FIGURE 2

Explains the role of lipid peroxidation as a mechanism toward neurodegeneration. Lipid peroxidation can occur either due to excessive production of reactive oxygen species (ROS), by the increased action of cyclooxygenase (COX), lipoxygenase (LOX), and cytochrome P450 (CYP) enzymes or by the involvement of transition metals. Once activated, lipid peroxidation induces the activation of phospholipases (each phospholipase carries out a different function). These phospholipases play a crucial role in neuronal inflammation. Using GSH as a coenzyme lipid peroxide can be reduced to the appropriate R‐OH or R‐CHO, GPx uses the results of lipid oxidation to produce hydroxyl acids catalytically. Adapted from Angelova et al. (2015). Created with BioRender.com.

FIGURE 3

Explains the role of DNA damage in neurodegeneration pathway. DNA damage can occur either during failed/ error in replicative process or as a consequence of oxidative or de‐aminating agents. Base mutation, base modification, double stranded break repair, or single stranded base repair all of it contributes to degeneration of motor neurons. Adapted from Kok et al. (2021). Created with BioRender.com.

FIGURE 4

Explains the implication of protein misfolding in neurodegenerative disorders. In circumstances where misfolded proteins are present, these are removed by the activation of proteosome activators, which mediates their clearance by proteasomal destruction. Newly produced proteins are stabilized by the action of endogenous chaperons. PTM inhibitors, protein cleavage inhibitors, and extrinsic chaperones are, however, implicated in regulating the removal of these misfolded proteins in neurological disorders, either through autophagy or by endogenous clearance. Adapted from Sweeney et al. (2017). Created with BioRender.com.