Nanoparticles in Combating Neuronal Dysregulated Signaling Pathways: Recent Approaches to the Nanoformulations of Phytochemicals and Synthetic Drugs Against Neurodegenerative Diseases

As the worldwide average life expectancy has grown, the prevalence of age related neurodegenerative diseases (NDDs) has risen dramatically. A progressive loss of neuronal function characterizes NDDs, usually followed by neuronal death. Inflammation, apoptosis, oxidative stress, and protein misfolding are critical dysregulated signaling pathways that mainly orchestrate neuronal damage from a mechanistic point. Furthermore, in afflicted families with genetic anomalies, mutations and multiplications of alpha-synuclein and amyloid-related genes produce some kinds of NDDs. Overproduction of such proteins, and their excessive aggregation, have been proven in various models of neuronal malfunction and death. In this line, providing multi-target therapies carried by novel delivery systems would pave the road to control NDDs through simultaneous modulation of such dysregulated pathways. Phytochemicals are multi-target therapeutic agents, which employ several mechanisms towards neuroprotection. Besides, the blood-brain barrier (BBB) is a critical issue in managing NDDs since it inhibits the accessibility of drugs to the brain in sufficient concentration. Besides, discovering novel delivery systems is vital to improving the efficacy, bioavailability, and pharmacokinetic of therapeutic agents. Such novel formulations are also employed to improve the drug's biodistribution, allow for the co-delivery of several medicines, and offer targeted intracellular delivery against NDDs. The present review proposes nanoformulations of phytochemicals and synthetic agents to combat NDDs by modulating neuroinflammation, neuroapoptosis, neuronal oxidative stress pathways and protein misfolding.

Automated summary

As the average life expectancy increases, age related neurodegenerative diseases (NDDs) have become more prevalent. These diseases are characterized by progressive loss of neuronal function and often followed by neuronal death. Dysregulated signaling pathways including inflammation, apoptosis, oxidative stress, and protein misfolding play crucial roles in neuronal damage. Genetic anomalies in affected families lead to mutations and multiplications of alpha-synuclein and amyloid-related genes, causing certain types of NDDs. Overproduction and aggregation of these proteins have been observed in various models of neuronal malfunction and death. Therefore, the development of multi-target therapies carried by novel delivery systems can be a promising approach to control NDDs by modulating these dysregulated pathways. Phytochemicals, which are multi-target therapeutic agents, offer neuroprotection through multiple mechanisms. However, the blood-brain barrier (BBB) poses challenges in treating NDDs as it limits the accessibility of drugs to the brain. Hence, the discovery of novel delivery systems is crucial to improve the efficacy, bioavailability, and pharmacokinetic of therapeutic agents.