Type 3 Diabetes: Cross Talk between Differentially Regulated Proteins of Type 2 Diabetes Mellitus and Alzheimer’s Disease

Mittal, Khyati; Mani, Ruchi Jakhmola; Katare, Deepshikha Pande

doi:10.1038/srep25589

Cited by 73 publications

(50 citation statements)

References 60 publications

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“…Growing clinical evidence points to a widespread AD-related systemic disorder characterized by severely affected peripheral parenchymal organs and blood in similar magnitude as the brain (54). Remarkably, the scope and features of AD-associated metabolic abnormalities resemble advanced pathology observed in obese and diabetic patients (55). These common aberrations led to the hypothesis that AD represents a unique form of diabetes.…”

Section: Load As a Systemic Metabolic Disordermentioning

confidence: 99%

A New Perspective on Alzheimer’s Disease as a Brain Expression of a Complex Metabolic Disorder

Polis

Samson

2019

Alzheimer’s Disease

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Alzheimer' s disease (AD) is an irredeemable chronic neurodegenerative disorder and the predominant cause of dementia. The disease progression is associated with the deposition of amyloid plaques and formation of neurofibrillary tangles in the brain, yet clinical dementia is the end and culminating stage of the enduring pathology. Recent evidence suggests that AD is characterized by distinctive abnormalities apparent on systemic, histological, macromolecular, and biochemical levels. Besides the well-described characteristic profuse neurofibrillary tangles, dystrophic neurites, and Aβ deposits, the AD pathology includes substantial neuronal loss, inflammation, extensive DNA damage, considerable mitochondrial malfunction, impaired energy metabolism, and chronic oxidative stress. Moreover, severe metabolic dysfunction leading to oxidative stress is a possible cause and hallmark of AD that is apparent decades before the disease manifestation. State-of-the-art metabolomics studies have proved that arginine and branched-chain amino acids metabolism disturbances accompany AD and contribute to its pathogenesis. Repetitive failures to find an efficient anti-amyloid or anti-Tau treatment, which would face the challenges of the complex AD pathology, led to the hypothesis that hyperphosphorylated Tau and deposited

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Section: Load As a Systemic Metabolic Disordermentioning

confidence: 99%

A New Perspective on Alzheimer’s Disease as a Brain Expression of a Complex Metabolic Disorder

Polis

Samson

2019

Alzheimer’s Disease

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“…In silico Interaction between proteins involved in DM and AD with emphasis on "type 3 diabetes" India 2016 (Mittal, Mani, & Katare, 2016) Molecular dynamic simulation approach to link DM to AD Israel 2016 (Baram, Atsmon-Raz, Ma, Nussinov, & Miller, 2016) Several studies have been carried out in this research area of growing link between diabetes and Alzheimer's in the interim of few years which is discussed here. Across the globe, various in vitro and in vivo studies using cell lines and animals like mice, rats, and monkeys, respectively, have been mentioned along with some studies carried out in humans.…”

Section: Studies Exploring Correlations Between Diabetes and Alzheimentioning

confidence: 99%

Cognitive dysfunction: A growing link between diabetes and Alzheimer's disease

Jash

Gondaliya

Kirave

et al. 2019

Drug Development Research

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Diabetes mellitus (DM) is a gradually rising metabolic disease which is currently affecting millions of people worldwide. Diabetes is associated with various complications like nephropathy, neuropathy, retinopathy, diabetic foot, cognitive impairment, and many more. Evidence suggests that cognitive dysfunction is a rising complication of diabetes which adversely affects the brain of patients suffering from diabetes. Age‐related memory impairment is a complication having its major effect on people suffering from diabetes and Alzheimer's. Patients suffering from diabetes are at two times higher risk of developing cognitive dysfunction as compared with normal individuals. Multiple factors which are involved in diabetes related complications are found to play a role in the development of neurodegeneration in Alzheimer's. The problem of insulin deficiency and insulin resistance is well reported in diabetes but there are many studies which suggest dysregulation of insulin levels as a reason behind the development of Alzheimer's. As the link between diabetes and Alzheimer disease (AD) is deepening, there is a need to understand the plausible tie‐ins between the two. Emerging role of major factors like insulin imbalance, advanced glycation end products and micro‐RNA's involved in diabetes and Alzheimer's have been discussed here. This review helps in understanding the plausible mechanism underlying the pathophysiology of amyloid beta (Aβ) plaque formation and tau hyperphosphorylation as well provides information about studies carried out in this area of research. The final thought is to enhance the scientific knowledge on this correlation and develop future therapeutics to treat the same.

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“…In 2005, Dr. Suzanne M de la Monte coined the term type 3 diabetes (T3D) to define a state of brain insulin resistance plus insulin deficiency that, in some cases, can overlap with type 2 diabetes mellitus (T2DM) [100,101]. In the last decade, many other researchers have backed up this hypothesis with other new discoveries and ground-breaking research projects [80,96,[102][103][104].…”

Section: The Metabolism Of Insulin In the Brainmentioning

confidence: 99%

Role of c-Jun N-Terminal Kinases (JNKs) in Epilepsy and Metabolic Cognitive Impairment

Busquets

Ettcheto

Cano

et al. 2019

IJMS

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Previous studies have reported that the regulatory function of the different c-Jun N-terminal kinases isoforms (JNK1, JNK2, and JNK3) play an essential role in neurological disorders, such as epilepsy and metabolic-cognitive alterations. Accordingly, JNKs have emerged as suitable therapeutic strategies. In fact, it has been demonstrated that some unspecific JNK inhibitors exert antidiabetic and neuroprotective effects, albeit they usually show high toxicity or lack therapeutic value. In this sense, natural specific JNK inhibitors, such as Licochalcone A, are promising candidates. Nonetheless, research on the understanding of the role of each of the JNKs remains mandatory in order to progress on the identification of new selective JNK isoform inhibitors. In the present review, a summary on the current gathered data on the role of JNKs in pathology is presented, as well as a discussion on their potential role in pathologies like epilepsy and metabolic-cognitive injury. Moreover, data on the effects of synthetic small molecule inhibitors that modulate JNK-dependent pathways in the brain and peripheral tissues is reviewed.

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Type 3 Diabetes: Cross Talk between Differentially Regulated Proteins of Type 2 Diabetes Mellitus and Alzheimer’s Disease

Cited by 73 publications

References 60 publications

A New Perspective on Alzheimer’s Disease as a Brain Expression of a Complex Metabolic Disorder

A New Perspective on Alzheimer’s Disease as a Brain Expression of a Complex Metabolic Disorder

Cognitive dysfunction: A growing link between diabetes and Alzheimer's disease

Role of c-Jun N-Terminal Kinases (JNKs) in Epilepsy and Metabolic Cognitive Impairment

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