scholarly journals Faculty Opinions recommendation of Molecular interaction between type 2 diabetes and Alzheimer's disease through cross-seeding of protein misfolding.

Author(s):  
Steven A Rosenzweig
2017 ◽  
Vol 22 (9) ◽  
pp. 1327-1334 ◽  
Author(s):  
I Moreno-Gonzalez ◽  
G Edwards III ◽  
N Salvadores ◽  
M Shahnawaz ◽  
R Diaz-Espinoza ◽  
...  

2020 ◽  
Vol 19 (6) ◽  
pp. 1233-1242
Author(s):  
Talib Hussain ◽  
Syed Mohd Danish Rizvi ◽  
Gehad M. Subaiea ◽  
Abulrahman Sattam Alanazi ◽  
Afrasim Moin

Purpose: To design dual inhibitors against Alzheimer’s disease (AD) and type 2 diabetes mellitus (T2DM) via pharmacoinformatics approach.Methods: Dual Drug Candidates (DDC) were designed and explored for their molecular interaction with several AD and T2DM targets. Pterostilbene, a natural anti-T2DM compound was coupled with different cholinesterase inhibitors to design DDC. Orisis Datawarrior online property calculator  tools, Autock 4.2 and Hex 5.1 were used to investigate the potency of all DDC relative to positive controls.Results: The study found that DDC2 (pterostilbene - methylene linker -octa hydro amino phenothiazine), DDC3 (pterostilbene - ethylene linker - N-phthalimide) and DDC5 (pterostilbene - carbonyl linker - 2-methyl-4-aminoquinoline) were the most promising out of all the DDCs. DDC2 showed strong molecular interaction with most of the AD and T2DM targets, including acetylcholinesterase, butrylcholinesterase, β-secretase, receptor for advanced glycation end products and ATP sensitive potassium channel, dipeptidyl peptidase IV and sodium glucose transport protien 2. The findings also revealed the amyloid anti-aggregation potential of DDC.Conclusion: The results show that DDC3 and DDC5 significantly interfer with the primary nucleation process of β amyloid. Thus, DDC2, DDC3 and DDC5 have strong anti-T2DM and anti-AD potential. Keywords: Type 2 Diabetes Mellitus, Alzheimer’s disease, Dual drug candidate, Amyloid-beta, Pterostilbene


2019 ◽  
Vol 7 (46) ◽  
pp. 7267-7282 ◽  
Author(s):  
Baiping Ren ◽  
Yanxian Zhang ◽  
Mingzhen Zhang ◽  
Yonglan Liu ◽  
Dong Zhang ◽  
...  

Misfolded protein aggregates formed by the same (homologous) or different (heterologous/cross) sequences are the pathological hallmarks of many protein misfolding diseases (PMDs) including Alzheimer's disease (AD) and type 2 diabetes (T2D).


2020 ◽  
Vol 16 ◽  
Author(s):  
Nataly Guzmán-Herrera ◽  
Viridiana C. Pérez-Nájera ◽  
Luis A. Salazar-Olivo

Background: Numerous studies have shown a significant association between type 2 diabetes mellitus (T2D) and Alzheimer's disease (AD), two pathologies affecting millions of people worldwide. Chronic inflammation and oxidative stress are two conditions common to these diseases also affecting the activity of the serpin alpha-1-antichymotrypsin (ACT), but a possible common role for this serpin in T2D and AD remains unclear. Objective: To explore the possible regulatory networks linking ACT to T2D and AD. Materials and Methods: A bibliographic search was carried out in PubMed, Med-line, Open-i, ScienceDirect, Scopus and SpringerLink for data indicating or suggesting association among T2D, AD, and ACT. Searched terms like “alpha-1-antichymotrypsin”, “type 2 diabetes”, “Alzheimer's disease”, “oxidative stress”, “pro-inflammatory mediators” among others were used. Moreover, common therapeutic strategies between T2D and AD as well as the use of ACT as a therapeutic target for both diseases were included. Results: ACT has been linked with development and maintenance of T2D and AD and studies suggest their participation through activation of inflammatory pathways and oxidative stress, mechanisms also associated with both diseases. Likewise, evidences indicate that diverse therapeutic approaches are common to both diseases. Conclusion: Inflammatory and oxidative stresses constitute a crossroad for T2D and AD where ACT could play an important role. In-depth research on ACT involvement in these two dysfunctions could generate new therapeutic strategies for T2D and AD.


Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1236
Author(s):  
Jesús Burillo ◽  
Patricia Marqués ◽  
Beatriz Jiménez ◽  
Carlos González-Blanco ◽  
Manuel Benito ◽  
...  

Type 2 diabetes mellitus is a progressive disease that is characterized by the appearance of insulin resistance. The term insulin resistance is very wide and could affect different proteins involved in insulin signaling, as well as other mechanisms. In this review, we have analyzed the main molecular mechanisms that could be involved in the connection between type 2 diabetes and neurodegeneration, in general, and more specifically with the appearance of Alzheimer’s disease. We have studied, in more detail, the different processes involved, such as inflammation, endoplasmic reticulum stress, autophagy, and mitochondrial dysfunction.


Author(s):  
Manel Ben Aissa ◽  
Cutler T. Lewandowski ◽  
Kiira M. Ratia ◽  
Sue H. Lee ◽  
Brian T. Layden ◽  
...  

2018 ◽  
Vol 56 (2) ◽  
pp. 833-843 ◽  
Author(s):  
Sudhanshu P. Raikwar ◽  
Sachin M. Bhagavan ◽  
Swathi Beladakere Ramaswamy ◽  
Ramasamy Thangavel ◽  
Iuliia Dubova ◽  
...  

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