Neurotrophic factors for disease-modifying treatments of Parkinson's disease: gaps between basic science and clinical st
- PDF / 3,839,778 Bytes
- 23 Pages / 595.276 x 790.866 pts Page_size
- 93 Downloads / 173 Views
REVIEW
Neurotrophic factors for disease‑modifying treatments of Parkinson’s disease: gaps between basic science and clinical studies Piotr Chmielarz1 · Mart Saarma2 Received: 20 December 2019 / Revised: 16 June 2020 / Accepted: 19 June 2020 © The Author(s) 2020
Abstract Background Neurotrophic factors are endogenous proteins promoting the survival of different neural cells. Therefore, they elicited great interest as a possible treatment for neurodegenerative disorders, including Parkinson’s Disease (PD). PD is the second most common neurodegenerative disorder, scientifically characterized more than 200 years ago and initially linked with motor abnormalities. Currently, the disease is viewed as a highly heterogeneous, progressive disorder with a long presymptomatic phase, and both motor and non-motor symptoms. Presently only symptomatic treatments for PD are available. Neurohistopathological changes of PD affected brains have been described more than 100 years ago and characterized by the presence of proteinaceous inclusions known as Lewy bodies and degeneration of dopamine neurons. Despite more than a century of investigations, it has remained unclear why dopamine neurons die in PD. Methods This review summarizes literature data from preclinical studies and clinical trials of neurotrophic factor based therapies for PD and discuss it from the perspective of the current understanding of PD biology. Results Newest data point towards dysfunctions of mitochondria, autophagy-lysosomal pathway, unfolded protein response and prion protein-like spreading of misfolded alpha-synuclein that is the major component of Lewy bodies. Yet, the exact chain of events leading to the demise of dopamine neurons is unclear and perhaps different in subpopulations of patients. Conclusions Gaps in our understanding of underlying disease etiology have hindered our attempts to find treatments able to slow down the progression of PD.
* Piotr Chmielarz chmiel@if‑pan.krakow.pl * Mart Saarma [email protected] 1
Department of Brain Biochemistry, Maj Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland
Institute of Biotechnology, HiLIFE, University of Helsinki, Helsinki, Finland
2
13
Vol.:(0123456789)
P. Chmielarz, M. Saarma
Graphic abstract
Keywords Parkinson’s disease · Neurotrophic factors · Translational research · Disease-modifying · Clinical trials Abbreviations 6-OHDA 6-Hydoxydopamine ARTN Artemin ASK1 Apoptosis signal-regulating kinase 1 ATF4 Activating transcription factor 4 ATF6 Activating transcription factor 6 BCL-2 B-cell lymphoma 2 anti-apoptotic protein BDNF Brain-derived neurotrophic factor BiP Binding immunoglobulin protein Caspases Cysteine-containing proteases that cleave substrates after aspartic acid CDNF Cerebral dopamine neurotrophic factor CHOP C/EBP homologous protein eIF2A Eukaryotic translation initiation factor 2A EC Encapsulated cell ER Endoplasmic reticulum
13
GBA β-Glucocerebrosidase GDNF Glial cell line-derived neurotrophic factor GFRα (1–4) GDNF Fa
Data Loading...
