The role of amyloidogenic proteins as a meeting point of type 2 diabetes and Parkinson's disease pathways

2017 ◽  
Vol 32 (2) ◽  
pp. 208-208 ◽  
Author(s):  
Samaneh Mohasel ◽  
Soheila Sobhani
2016 ◽  
Vol 113 (44) ◽  
pp. 12473-12477 ◽  
Author(s):  
Istvan Horvath ◽  
Pernilla Wittung-Stafshede

In type-2 diabetes (T2D) and Parkinson’s disease (PD), polypeptide assembly into amyloid fibers plays central roles: in PD, α-synuclein (aS) forms amyloids and in T2D, amylin [islet amyloid polypeptide (IAPP)] forms amyloids. Using a combination of biophysical methods in vitro we have investigated whether aS, IAPP, and unprocessed IAPP, pro-IAPP, polypeptides can cross-react. Whereas IAPP forms amyloids within minutes, aS takes many hours to assemble into amyloids and pro-IAPP aggregates even slower under the same conditions. We discovered that preformed amyloids of pro-IAPP inhibit, whereas IAPP amyloids promote, aS amyloid formation. Amyloids of aS promote pro-IAPP amyloid formation, whereas they inhibit IAPP amyloid formation. In contrast, mixing of IAPP and aS monomers results in coaggregation that is faster than either protein alone; moreover, pro-IAPP can incorporate aS monomers into its amyloid fibers. From this intricate network of cross-reactivity, it is clear that the presence of IAPP can accelerate aS amyloid formation. This observation may explain why T2D patients are susceptible to developing PD.


Diabetes Care ◽  
2007 ◽  
Vol 30 (4) ◽  
pp. 842-847 ◽  
Author(s):  
G. Hu ◽  
P. Jousilahti ◽  
S. Bidel ◽  
R. Antikainen ◽  
J. Tuomilehto

2021 ◽  
Author(s):  
Dilan Athauda ◽  
James Evans ◽  
Anna Wernick ◽  
Gurvir Virdi ◽  
Minee Liane-Choi ◽  
...  

Importance: Type 2 diabetes (T2DM) is an established risk factor for developing Parkinson's disease (PD) but its effect on disease progression is not well understood. Objective: To examine the effects of co-morbid T2DM on Parkinson's disease progression and quality of life. Design: We analysed data from the Tracking Parkinson's study, a large multi-centre prospective study in the UK. Participants: The study included 1930 adults with recent onset PD, recruited between February 2012 and May 2014, and followed up regularly thereafter. Exposure: A diagnosis of pre-existing T2DM was based on self-report at baseline. After controlling for confounders, an evaluation of how T2DM affects PD was performed by comparing symptom severity scores; and analyses using multivariable mixed models was used to determine the effects of T2DM on Parkinson's disease progression. Main Outcomes and Measures: The impact of T2DM on Parkinsons disease severity was derived from scores collected using the Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Non-Motor Symptoms Scale (NMSS), Montreal Cognitive Assessment (MoCA), Questionnaire for impulsive-compulsive disorders in PD (QUIP), Leeds Anxiety and Depression Scale (LADS), and Schwab and England ADL scale. Results: We identified 167 (8.7%) patients with PD and T2DM (PD+T2DM) and 1763 (91.3%) with PD without T2DM (PD). Patients with T2DM had more severe motor symptoms, as assessed by MDS-UPDS III 25.8 (0.9) vs 22.5 (0.3) p=0.002, had significantly faster motor symptom progression over time (p=0.012), and T2DM was an independent predictor for the development of substantial gait impairment (HR 1.55, CI 1.07-2.23, p=0.020). Patients were more likely to have loss of independence (OR 2.08, CI 1.34-3.25, p=0.001); and depression (OR 1.62, CI 1.10-2.39, p=0.015), and developed worsening mood (p=0.041) over time compared to the PD group. T2DM was also an independent predictor for the development mild cognitive impairment (HR 1.7, CI 1.24-2.51, p=0.002) over time Conclusions and relevance: T2DM is associated with faster disease progression in PD, highlighting an interaction between these two diseases. As it is a potentially modifiable, metabolic state, with multiple peripheral and central targets for intervention, it may represent a target for ameliorating parkinsonian symptoms, and progression to disability and dementia.


2021 ◽  
Author(s):  
Harneek Chohan ◽  
Konstantin Senkevich ◽  
Radhika K. Patel ◽  
Jonathan P. Bestwick ◽  
Benjamin M. Jacobs ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document