Receptor tyrosine kinases (RTKs) consociate in regulatory clusters in Alzheimer’s disease and type 2 diabetes

Majumder, Piyali; Roy, Kasturi; Bagh, Sangram; Mukhopadhyay, Debashis

doi:10.1007/s11010-019-03560-5

Cited by 13 publications

(16 citation statements)

References 39 publications

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“…Up until our recent work, Insulin Receptor (IR) was the only RTK known to be involved in the signaling of both diseases. Profiling the activities of other RTKs in the two diseases opened up a larger picture and the toxic effects of both Aβ and Amylin oligomers were predicted to have impacts on other receptor tyrosine kinases (7). Amongst all the common RTKs, ALK and RYK were the two showing similar levels of deactivation in all working models of AD and T2D (7).…”

Section: Discussionmentioning

confidence: 99%

“…Profiling the activities of other RTKs in the two diseases opened up a larger picture and the toxic effects of both Aβ and Amylin oligomers were predicted to have impacts on other receptor tyrosine kinases (7). Amongst all the common RTKs, ALK and RYK were the two showing similar levels of deactivation in all working models of AD and T2D (7). ALK, a member of insulin receptor superfamily, is commonly known for its involvement in many cancer types, especially in non-small-cell lung cancer (NSCLC) (50).…”

Section: Discussionmentioning

confidence: 99%

“…Insulin receptor (IR), a receptor tyrosine kinase (RTK), further links both of them exhibiting resistance to insulin signaling and other metabolic disbalances. Our recent study lists the differential activities of several human RTKs in post-mortem brain tissues of AD patients and liver tissues of T2D patients and categorizes them into functional and regulational clusters (6). Two RTKs, Anaplastic lymphoma kinase (ALK) and receptor-like tyrosine kinase (RYK), functionally behave in a similar fashion in both the disease situations (7).…”

Section: Introductionmentioning

confidence: 99%

“…Our recent study lists the differential activities of several human RTKs in post-mortem brain tissues of AD patients and liver tissues of T2D patients and categorizes them into functional and regulational clusters (6). Two RTKs, Anaplastic lymphoma kinase (ALK) and receptor-like tyrosine kinase (RYK), functionally behave in a similar fashion in both the disease situations (7). Both ALK and RYK are involved in the regulation of Wnt/β-Catenin signaling (8)(9)(10), which behaves aberrantly in both AD and T2D (11).…”

Section: Introductionmentioning

confidence: 99%

“…Both ALK and RYK are involved in the regulation of Wnt/β-Catenin signaling (8)(9)(10), which behaves aberrantly in both AD and T2D (11). In a recent study both ALK and RYK were shown to have significantly decreased activities in AD and T2D conditions (7).…”

Section: Introductionmentioning

confidence: 99%

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Transcriptional regulator PAX4 links Receptor Tyrosine Kinases (RTKs) and cytoskeleton stability in Alzheimer’s disease and type 2 diabetes

Majumder

Chanda

Das

et al. 2020

Preprint

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Alzheimer's Disease (AD) and Type 2 Diabetes (T2D) share a common hallmark of insulin resistance. Besides Insulin Receptor (IR), two non-canonical RTKs, ALK and RYK, exhibit significant and consistent functional downregulation in post-mortem AD and T2D tissues. Incidentally, both have Grb2 as a common downstream adapter and NOX4 as a common ROS producing factor. Here we show that Grb2 and NOX4 play critical roles in reducing the severity of both the diseases. The study demonstrates that the abundance of Grb2 in degenerative conditions, in conjunction with NOX4, reverse cytoskeletal degradation by counterbalancing the network of small GTPases. PAX4, a transcription factor for both Grb2 and NOX4, emerges as the key link between the common pathways of AD and T2D. Both ALK and RYK downregulation elevate the PAX4 level by reducing its suppressor ARX via Wnt/β-Catenin signaling pathway. For the first time, this study brings together RTKs other than Insulin Receptor (IR), their common transcription factor PAX4 and both AD and T2D pathologies on a common regulatory platform.

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Section: Discussionmentioning

confidence: 99%