Drug Development against Parkinson’s Disease
Subjects: Neurosciences
Contributors:

Parkinson’s disease (PD) is currently the second most common neurodegenerative disease among the older population. The main problem in the treatment is that the exact etiology of the disease is not known, and it is not known what exactly initiates the neuronal damage process. There is still no drug that would effectively cure the disease. However, 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.

  • computer modeling
  • drugs
  • in vitro models
  • in vivo models
  • neurodegeneration
  • Parkinson’s disease

Parkinson’s disease is a progressive neurodegenerative disorder characterized by the death of nerve cells mainly in the substantia nigra of the brain. Due to the complexity of the disease, the etiology of PD is still not fully understood. It is found that environmental and genetic factors play an important role in its development. 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. The current knowledge of molecular targets is still incomplete, but new reports on them are constantly being sought [1][2]. 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 reflect pathogenic changes in the brain is a key aspect of this research. For this reason, it is proposed that the cell and animal models for PD studies reflect as much as possible the human pathophysiological and behavioral aspects of the disease.Examples of such in vitro models are the SH-SY5Y line, PC12, the LUHMES cell line as well as the 3D cultures that best reflect the complex biological mechanisms and processes of the human body. While, examples of in vivo models are toxin / pesticide models (e.g. 6-hydroxydopamine, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, rotenone) and genetic models (e.g. α-synuclein, LRRK2) [3]

In addition, computer-assisted drug design methods are a promising approach to developing effective compounds with potential therapeutic effects [3][4].

Therefore, thanks to advanced technology and the use of appropriate research models, it is possible to thoroughly understand the mechanisms of PD and to develop and test new drugs that may be effective in the treatment of PD.

 
 
 

This entry is adapted from 10.3390/biom11060897

References

  1. Rozpędek-Kamińska, W.; Siwecka, N.; Wawrzynkiewicz, A.; Wojtczak, R.; Pytel, D.; Diehl, J.A.; Majsterek, I. The PERK-Dependent Molecular Mechanisms as a Novel Therapeutic Target for Neurodegenerative Diseases. Int. J. Mol. Sci. 2020, 21, 2108.
  2. Parkinson’s Disease: Etiology, Neuropathology, and Pathogenesis—Parkinson’s Disease—NCBI Bookshelf. Available online: (accessed on 16 April 2021).
  3. Ikeda, K.; Kurokawa, M.; Aoyama, S.; Kuwana, Y. Neuroprotection by adenosine A2A receptor blockade in experimental models of Parkinson’s disease. J. Neurochem. 2002, 80, 262–270.
  4. Aryati, W.D.; Salamah, N.N.; Syahdi, R.R.; Yanuar, A. The Role and Development of the Antagonist of Adenosine A2A in Parkinson’s Disease. In Neurodegeneration; Chuen-Chung Chang, R., Ho, Y.-S., Eds.; IntechOpen: London, UK, 2019; ISBN 978-1-78984-737-6.
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