Current Approaches and Tools Used in Drug Development against Parkinson's Disease.

Oliwia Koszła,Angelika Grudzińska,Agnieszka A Kaczor,Dariusz Matosiuk,Agata Zięba,Piotr Stępnicki

doi:10.3390/biom11060897

Oliwia Koszła, Angelika Grudzińska + Show 4 more

Open Access

https://doi.org/10.3390/biom11060897

Copy DOI

Abstract

Parkinson’s disease is a progressive neurodegenerative disorder characterized by the death of nerve cells in the substantia nigra of the brain. The treatment options for this disease are very limited as currently the treatment is mainly symptomatic, and the available drugs are not able to completely stop the progression of the disease but only to slow it down. There is still a need to search for new compounds with the most optimal pharmacological profile that would stop the rapidly progressing disease. An increasing understanding of Parkinson’s pathogenesis and the discovery of new molecular targets pave the way to develop new therapeutic agents. The use and selection of appropriate cell and animal models that better reflect pathogenic changes in the brain is a key aspect of the research. In addition, computer-assisted drug design methods are a promising approach to developing effective compounds with potential therapeutic effects. In light of the above, in this review, we present current approaches for developing new drugs for Parkinson’s disease.

Highlights

The diagnosis is based on the finding of at least two symptoms from among: tremor, rigidity, bradykinesia and postural instability, and is further confirmed by performing a histopathological examination which indicates the presence of Lewy bodies—protein aggregates composed of alpha-synuclein—which is a useful biomarker for in vitro research
The accumulated proteins cause degeneration of dopaminergic neurons, especially in the substantia nigra (SN) area, which reduces the concentration of dopamine and weakens the dopaminergic transmission, leading to the motor symptoms characteristic of Parkinson’s disease (PD)
Age is the biggest risk factor: over 60 years of age, the risk of developing the disease fluctuates within 2%, while above 80 years, it increases to 4%

Summary

Introduction

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. It has been shown that inhibition of these enzymes increases the level of dopamine in the brain by preventing its degradation This has a positive effect on the motor and non-motor symptoms of PD, especially in the early stages of the disease [5]. Blockade of PTB has been shown to lead to the conversion of astrocytes into dopaminergic neurons, which restores normal dopamine transmission. This gives hope for an effective treatment that can cure PD permanently [6]. Standard treatment of PD focuses on increasing the levels of dopamine in the brain and preventing it from breaking down This treatment does not inhibit the progression of the disease. Scientists are still trying to develop more effective pharmacotherapy by using new molecular targets based on relevant in vitro and in vivo models, and by using computer-aided design of drugs and other particles

In Vitro Models for Parkinson’s Disease Studies

In Vivo Models for Parkinson’s Disease Studies

Computational Approaches Used in the Development of Novel Drugs against

Recent Reports of Novel Agents against Parkinson’s Disease

Findings

Conclusions