International Journal of Nanomedicine (Jan 2022)
Nanoparticles in Combating Neuronal Dysregulated Signaling Pathways: Recent Approaches to the Nanoformulations of Phytochemicals and Synthetic Drugs Against Neurodegenerative Diseases
Abstract
Sajad Fakhri,1 Sadaf Abdian,2,* Seyede Nazanin Zarneshan,2,* Seyed Zachariah Moradi,1,3 Mohammad Hosein Farzaei,1 Mohammad Abdollahi4,5 1Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran; 2Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran; 3Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran; 4Toxicology and Diseases Group, Pharmaceutical Sciences Research Center (PSRC), The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran; 5Department of Toxicology and Pharmacology, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran*These authors contributed equally to this workCorrespondence: Mohammad Hosein Farzaei; Mohammad Abdollahi Email [email protected]; [email protected]: 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 α-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.Keywords: neuroprotection, apoptosis, inflammation, oxidative stress, novel delivery system, therapeutic target, pharmacology
