Patient-derived iPSCs, a reliable in vitro model for the investigation of Alzheimer’s disease

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Asiamah Ernest Amponsah ◽  
Ruiyun Guo ◽  
Desheng Kong ◽  
Baofeng Feng ◽  
Jingjing He ◽  
...  

Abstract Alzheimer’s disease (AD) is a neurodegenerative disease and a common cause of dementia among elderly individuals. The disease is characterized by progressive cognitive decline, accumulation of senile amyloid plaques and neurofibrillary tangles, oxidative stress, and inflammation. Human-derived cell models of AD are scarce, and over the years, non-human-derived models have been developed to recapitulate clinical AD, investigate the disease’s pathogenesis and develop therapies for the disease. Several pharmacological compounds have been developed for AD based on findings from non-human-derived cell models; however, these pharmacological compounds have failed at different phases of clinical trials. This necessitates the application of human-derived cell models, such as induced pluripotent stem cells (iPSCs) in their optimized form in AD mechanistic studies and preclinical drug testing. This review provides an overview of AD and iPSCs. The AD-relevant phenotypes of iPSC-derived AD brain cells and the usefulness of iPSCs in AD are highlighted. Finally, the various recommendations that have been made to enhance iPSC/AD modelling are discussed.

Biochemistry ◽  
1999 ◽  
Vol 38 (28) ◽  
pp. 8972-8980 ◽  
Author(s):  
James D. Harper ◽  
Stanislaus S. Wong ◽  
Charles M. Lieber ◽  
Peter T. Lansbury

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Aslina Pahrudin Arrozi ◽  
Siti Nur Syazwani Shukri ◽  
Wan Zurinah Wan Ngah ◽  
Yasmin Anum Mohd Yusof ◽  
Mohd Hanafi Ahmad Damanhuri ◽  
...  

2016 ◽  
Vol 12 ◽  
pp. P451-P451
Author(s):  
Victor Junji Yamamoto ◽  
Vanessa de Jesus de Paula ◽  
Giancarlo de Mattos Cardillo ◽  
Orestes Vicente Forlenza ◽  
Wagner Farid Gattaz ◽  
...  

2021 ◽  
Vol 43 (1) ◽  
pp. 197-214
Author(s):  
Serena Silvestro ◽  
Luigi Chiricosta ◽  
Agnese Gugliandolo ◽  
Renato Iori ◽  
Patrick Rollin ◽  
...  

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and represents the most common form of senile dementia. Autophagy and mitophagy are cellular processes that play a key role in the aggregation of β-amyloid (Aβ) and tau phosphorylation. As a consequence, impairment of these processes leads to the progression of AD. Thus, interest is growing in the search for new natural compounds, such as Moringin (MOR), with neuroprotective, anti-amyloidogenic, antioxidative, and anti-inflammatory properties that could be used for AD prevention. However, MOR appears to be poorly soluble and stable in water. To increase its solubility MOR was conjugated with α-cyclodextrin (MOR/α-CD). In this work, it was evaluated if MOR/α-CD pretreatment was able to exert neuroprotective effects in an AD in vitro model through the evaluation of the transcriptional profile by next-generation sequencing (NGS). To induce the AD model, retinoic acid-differentiated SH-SY5Y cells were exposed to Aβ1-42. The MOR/α-CD pretreatment reduced the expression of the genes which encode proteins involved in senescence, autophagy, and mitophagy processes. Additionally, MOR/α-CD was able to induce neuronal remodeling modulating the axon guidance, principally downregulating the Slit/Robo signaling pathway. Noteworthy, MOR/α-CD, modulating these important pathways, may induce neuronal protection against Aβ1-42 toxicity as demonstrated also by the reduction of cleaved caspase 3. These data indicated that MOR/α-CD could attenuate the progression of the disease and promote neuronal repair.


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