scholarly journals Alpha-synuclein research: defining strategic moves in the battle against Parkinson’s disease

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Luis M. A. Oliveira ◽  
Thomas Gasser ◽  
Robert Edwards ◽  
Markus Zweckstetter ◽  
Ronald Melki ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Disease ◽  
Alpha Synuclein ◽  
Position Paper ◽  
Future Research ◽  
Slow Disease Progression ◽  
Critical Areas ◽  
The Us ◽  
Important Player

AbstractWith the advent of the genetic era in Parkinson’s disease (PD) research in 1997, α-synuclein was identified as an important player in a complex neurodegenerative disease that affects >10 million people worldwide. PD has been estimated to have an economic impact of $51.9 billion in the US alone. Since the initial association with PD, hundreds of researchers have contributed to elucidating the functions of α-synuclein in normal and pathological states, and these remain critical areas for continued research. With this position paper the authors strive to achieve two goals: first, to succinctly summarize the critical features that define α-synuclein’s varied roles, as they are known today; and second, to identify the most pressing knowledge gaps and delineate a multipronged strategy for future research with the goal of enabling therapies to stop or slow disease progression in PD.

scholarly journals Alpha-Synuclein aggregation in Parkinson’s Disease

2021 ◽  
Vol 2 (2) ◽  
Author(s):  
Rheia Reader
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Disease ◽  
Symptom Relief ◽  
Three Dimensional ◽  
Alpha Synuclein ◽  
Dimensional Structure ◽  
Management Options ◽  
Animal Models Of Disease ◽  
Early Disease Detection

The ability of polypeptides to fold into a functional, three-dimensional structure forms the basis of normal cellular and organ function, however, when this fundamental process goes awry it forms the basis of neurodegenerative diseases. Nearly 1 in 6 people have a neurological condition and these diseases can be debilitating and incurable. Parkinson’s Disease (PD) is the second most common neurodegenerative disease that is known as a movement disorder, but that is also characterized by additional non-motor associated symptoms. The pathophysiological hallmark of PD is the misfolding and aggregation of the protein α-synuclein (α-Syn) and the accompanying loss of neurons that produce dopamine in the brain. There are currently no proven therapies for PD and management options consist of symptom relief. Through the development of multidisciplinary approaches (including nuclear magnetic resonance, high-resolution imaging and animal models of disease), scientists have made great strides in our understanding of the chemical, genetic and molecular basis of PD. Although it is commonly accepted that aggregation of α-Syn is key in the pathogenesis of PD, the extent to which its aggregation plays a causal role in neurodegeneration is still a matter of intense investigation. This review will provide a critical assessment of the importance of α-Syn aggregation in PD and discuss the experimental approaches and current and future therapies for this neurodegenerative disease. Expanding our knowledge of the role of protein aggregation in the pathophysiology of PD is critical for the identification of biomarkers for early disease detection, as well as for the development of novel and specific therapeutic approaches.

scholarly journals C-Abl Inhibition; A Novel Therapeutic Target for Parkinson's Disease

2018 ◽  
Vol 17 (1) ◽  
pp. 14-21 ◽  
Author(s):  
Abdelrahman Ibrahim Abushouk ◽  
Ahmed Negida ◽  
Rasha Abdelsalam Elshenawy ◽  
Hossam Zein ◽  
Ali M. Hammad ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Drug Targets ◽  
Experimental Studies ◽  
Lewy Bodies ◽  
Alpha Synuclein ◽  
Current Evidence ◽  
Future Research ◽  
Neuroprotective Effects ◽  
Human Trial

Parkinson's disease (PD) is the most prevalent movement disorder in the world. The major pathological hallmarks of PD are death of dopaminergic neurons and the formation of Lewy bodies. At the moment, there is no cure for PD; current treatments are symptomatic. Investigators are searching for neuroprotective agents and disease modifying strategies to slow the progress of neurodegeneration. However, due to lack of data about the main pathological sequence of PD, many drug targets failed to provide neuroprotective effects in human trials. Recent evidence suggests the involvement of C-Abelson (c-Abl) tyrosine kinase enzyme in the pathogenesis of PD. Through parkin inactivation, alpha synuclein aggregation, and impaired autophagy of toxic elements. Experimental studies showed that (1) c-Abl activation is involved in neurodegeneration and (2) c-Abl inhibition shows neuroprotective effects and prevents dopaminergic neuronal' death. Current evidence from experimental studies and the first in-human trial shows that c-Abl inhibition holds the promise for neuroprotection against PD and therefore, justifies the movement towards larger clinical trials. In this review article, we discussed the role of c-Abl in PD pathogenesis and the findings of preclinical experiments and the first in-human trial. In addition, based on lessons from the last decade and current preclinical evidence, we provide recommendations for future research in this area.

scholarly journals The Past, Present, and Future of Parkinson's Disease Treatment

2020 ◽  
Vol 5 (4) ◽  
Author(s):  
Soyeon Park
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Viral Vectors ◽  
Motor Fluctuation ◽  
Alpha Synuclein ◽  
Future Research ◽  
Late 20Th Century ◽  
Internal Globus Pallidus ◽  
Gene Therapies ◽  
Neuroprotective Therapies

Parkinson’s Disease was first introduced by James Parkinson in 1817. Since then, major strides have been made in the development of its treatment. Early treatments were dominated by traditional and complementary therapies, which were largely serendipitous and observation-based. Especially, the use of anticholinergics by Jean-Martin Charcot and his student Ordenstein prevailed in the late 20th century. Current drug-based therapies manifest in the form of levodopa accompanied by dopamine agonist, COMT inhibitor, or MAO-B inhibitor, for the purpose of reducing the levodopa-induced symptom fluctuation. In terms of surgical treatment, while ablative surgeries in the brain have been abandoned due to high mortality rate in the late 1900s, Deep Brain Stimulation in the subthalamic nucleus or internal globus pallidus has mostly replaced ablative surgeries since its introduction in 1987. Current research topics include non-dopaminergic agents for motor fluctuation reduction, transplantation of dopaminergic neurons, gene therapies using viral vectors, reduction of alpha-synuclein neurotoxicity, and neuroprotective therapies. Especially, due to the fact that the etiology of the disease is yet to be elucidated, neuroprotective therapies aimed at slowing or stopping disease progression are of particular interest. It is suggested that future research should aim towards clarifying the cause of the disease, for the development of a treatment that can permanently halt or reverse Parkinson’s Disease-related neurodegeneration.

scholarly journals The Role of Mental Imagery in Parkinson’s Disease Rehabilitation

2021 ◽  
Vol 11 (2) ◽  
pp. 185
Author(s):  
Amit Abraham ◽  
Ryan P. Duncan ◽  
Gammon M. Earhart
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Disease ◽  
Mental Imagery ◽  
Future Research ◽  
Motor Rehabilitation ◽  
Research Directions ◽  
Current Therapies ◽  
Future Research Directions

Parkinson’s disease (PD) is a disabling neurodegenerative disease whose manifestations span motor, sensorimotor, and sensory domains. While current therapies for PD include pharmacological, invasive, and physical interventions, there is a constant need for developing additional approaches for optimizing rehabilitation gains. Mental imagery is an emerging field in neurorehabilitation and has the potential to serve as an adjunct therapy to enhance patient function. Yet, the literature on this topic is sparse. The current paper reviews the motor, sensorimotor, and sensory domains impacted by PD using gait, balance, and pain as examples, respectively. Then, mental imagery and its potential for PD motor and non-motor rehabilitation is discussed, with an emphasis on its suitability for addressing gait, balance, and pain deficits in people with PD. Lastly, future research directions are suggested.

scholarly journals Parkinson's disease (PD) is the most common neurodegenerative disease

2015 ◽  
Vol 22 (2) ◽  
pp. 14-17 ◽  
Author(s):  
P. A. Andoskin ◽  
A. K. Emelyanov ◽  
M. A. Nikolaev ◽  
K. A. Senkevich ◽  
V. P. Shilin ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Disease ◽  
Neurological Disorders ◽  
Alpha Synuclein ◽  
Control Group ◽  
Blood Fraction ◽  
Lymphocyte Fraction

Metabolic impairment of alpha-synuclein protein is considered to be the central event in PDpathogenesis. Recent studies explored usage of alpha-synuclein in peripheral fluids as a biomarker of PD, however alpha-synuclein level in the CSF and plasma is considered to be affected by hemolysis. In order to avoid contamination of a lymphocyte fraction by erythrocytes, we have proposed an algorithm based on measurements of alpha-synuclein levels in the homogeneous CD45+ cell blood fraction. For this study we formed a group of PD patients (N=14) and a control group without the neurological disorders (N=17). We found an increase in the level of the total alpha-synuclein in CD45+ cells of PD patients compared to controls (p = 0,04), and revealed a direct correlation between the level of dopamine in plasma and level of total alpha-synuclein in CD45+ cells in the control group (r=0,71, p = 0,007).The level of alpha-synuclein in CD45+ cells could be suggested as possible PD biomarker.

Sign in / Sign up

Export Citation Format

Share Document