A Potential Innovative Therapy for Parkinson’s Disease: Selective Destruction of the Pathological Assemblies of Alpha-Synuclein
With the aging of the population, Parkinson’s disease poses a serious socio-economic problem; there is no effective therapy that can arrest/revert the progression of the disease. The hallmarks of Parkinson’s disease and other synucleinopathies are the disordered alpha-synuclein and TPPP/p25. These p...
Guardado en:
| Autores principales: | , , , |
|---|---|
| Formato: | Capítulo de libro |
| Lenguaje: | inglés |
| Publicado: |
IntechOpen
2021
|
| Materias: | |
| Acceso en línea: | https://www.intechopen.com/chapters/74933 |
| Etiquetas: |
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| Sumario: | With the aging of the population, Parkinson’s disease poses a serious socio-economic problem; there is no effective therapy that can arrest/revert the progression of the disease. The hallmarks of Parkinson’s disease and other synucleinopathies are the disordered alpha-synuclein and TPPP/p25. These proteins have neomorphic moonlighting characteristics by displaying both physiological and pathological functions. Physiologically TPPP/p25 regulates the dynamics/stability of the microtubules and is crucial for oligodendrocyte differentiation; while alpha-synuclein is involved in neuronal plasticity modulation and synaptic vesicle pool maintenance. In healthy brain, alpha-synuclein and TPPP/p25 occur predominantly in neurons and oligodendrocytes, respectively; however, they are co-enriched and co-localized in both cell types in brain inclusions in the cases of Parkinson’s disease and multiple system atrophy, respectively. The pathomechanisms of these diseases are largely unknown; the fatal species are the small, soluble homo- and hetero-associations of alpha-synuclein. These proteins with their high conformational plasticity and chameleon feature are challenging drug targets. Nevertheless, the contact surface of TPPP/p25-alpha-synuclein assemblies has been validated as a specific drug target. This new strategy with innovative impact, namely targeting the interface of the TPPP/p25-alpha-synuclein complex, could contribute to the development of anti-Parkinson drugs with unique specificity. |
|---|---|
| ISBN: | 978-1-83968-843-0 |
| DOI: | 10.5772/intechopen.97271 |