Type 2 diabetes mellitus and Alzheimer’s disease

Barbagallo, Mario; Domínguez, Ligia J.

doi:10.4239/wjd.v5.i6.889

Cited by 217 publications

(135 citation statements)

References 34 publications

Supporting

Mentioning

130

Contrasting

Unclassified

Order By: Relevance

“…However, it is now widely recognized that AD and T2D share many pathophysiological features including increased oxidative stress and amyloid aggregation. [1][2][3][4] Amyloid β (Aβ) is the component of the amyloid deposits in the AD brain, 5) while the component of the amyloidogenic peptide deposit in the diabetic pancreatic islets of Langerhans is identified as islet amyloid polypeptide (IAPP), a 37-amino acid peptide. 6,7) Although the amino acid sequences of amyloidogenic proteins are diverse, they all adopt a similar structure in aggregates called cross-β-spine.…”

mentioning

confidence: 99%

Inhibitory Activities of Antioxidant Flavonoids from <i>Tamarix gallica</i> on Amyloid Aggregation Related to Alzheimer’s and Type 2 Diabetes Diseases

Hmidene

Hanaki

Murakami

et al. 2017

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

The prevention of amyloid aggregation is promising for the treatment of age-related diseases such as Alzheimer's (AD) and type 2 diabetes (T2D). Ten antioxidant flavonoids isolated from the medicinal halophyte Tamarix gallica were tested for their amyloid aggregation inhibition potential. Glucuronosylated flavonoids show relatively strong inhibitory activity of Amyloid β (Aβ) and human islet amyloid polypeptide (hIAPP) aggregation compared to their aglycone analogs. Structure-activity relationship of the flavonoids suggests that the catechol moiety is important for amyloid aggregation inhibition, while the methylation of the carboxyl group in the glucuronide moiety and of the hydroxyl group in the aglycone flavonoids decreased it.Key words amyloid aggregation; glucuronosylated flavonoid; Tamarix gallica; Alzheimer's disease; type 2 diabetes The incidence of both disturbances Alzheimer's disease (AD) and type 2 diabetes (T2D) is increasing and has become a major public health concern in many industrialized countries. Despite intense research, best strategies to treat/prevent these costly diseases are still under investigation. However, it is now widely recognized that AD and T2D share many pathophysiological features including increased oxidative stress and amyloid aggregation. 1-4)Amyloid β (Aβ) is the component of the amyloid deposits in the AD brain, 5) while the component of the amyloidogenic peptide deposit in the diabetic pancreatic islets of Langerhans is identified as islet amyloid polypeptide (IAPP), a 37-amino acid peptide. 6,7) Although the amino acid sequences of amyloidogenic proteins are diverse, they all adopt a similar structure in aggregates called cross-β-spine.8) Extensive studies in the past years have found that, similar to Aβ 1-42 , IAPP forms early intermediate assemblies as spherical oligomers 9,10) that are recognized by soluble Aβ oligomers antibody, 11) implicating that these oligomers possess a common folding pattern or conformation.4) The similarities in Aβ 1-42 and IAPP oligomers can be used to investigate the prevention of oxidative stress and amyloid aggregation inhibition related to AD and T2D, since potent therapeutic agents such as antioxidants with a catechol moiety, proved to inhibit Aβ aggregation, 12-16) may play a key role inhibiting the aggregation of human IAPP (hIAPP) in case of patients with diabetes.The powerful antioxidant activity of the medicinal halophyte Tamarix gallica L. has been reported as exhibiting a remarkable spectrum of biochemical and pharmacological activities. Although traditionally used for the treatment of various liver disorders and marketed as a herbal medicine in many countries, [17][18][19] there have been no reports on the use of this plant for the treatment or prevention of AD or T2D. Therefore, the aim of this research is to investigate the protective effect of T. gallica towards both disturbances by isolation and identification of the Aβ and hIAPP aggregation inhibitors with antioxidant potential. MATERIALS AND METHODS MaterialsThe aerial par...

show abstract

mentioning

confidence: 99%

Inhibitory Activities of Antioxidant Flavonoids from <i>Tamarix gallica</i> on Amyloid Aggregation Related to Alzheimer’s and Type 2 Diabetes Diseases

Hmidene

Hanaki

Murakami

et al. 2017

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

show abstract

“…Unfortunately, such concomitant therapy has been explicitly mentioned in inclusion/exclusion criteria in several studies only [96,110,111] (Table 3), while no data have been provided for comorbidity of diabetes mellitus (Table 3), a disease which itself carries a risk for AD development [128,129].…”

Section: Concomitant Drug Therapy the Largest Was The Study Conductementioning

confidence: 99%

Evaluating the Role of Hormone Therapy in Postmenopausal Women with Alzheimer’s Disease

Osmanovic-Barilar

Salkovic-Petrisi

2016

Drugs Aging

View full text Add to dashboard Cite

Hormone therapy (HT) is prescribed during or after menopausal transition to replace the decline in estrogen and progesterone levels. While some studies indicate that estrogen and progesterone depletion in postmenopausal women might carry a significant risk for developing sporadic Alzheimer's disease (sAD), which may be reduced by HT, recent clinical trials oppose this beneficial effect. This review points to possible reasons for these mixed data by considering the issues of both preclinical and clinical trials, in particular the representativeness of animal models, timing of HT initiation, type of HT (different types of estrogen compound, estrogen monotherapy versus estrogen-progesterone combined therapy), mode of drug delivery (subcutaneous, transdermal, oral or intramuscular) and hormone dosage used, as well as the heterogeneity of the postmenopausal population in clinical trials (particularly considering their sAD stage, anti-AD therapy and hysterectomy status). Careful planning of future preclinical and clinical HT interventional studies might help to elucidate the effect of HT on cognitive status in postmenopausal women with sAD, which will eventually contribute to more effective sAD prevention and treatment. Key points:• The influence of hormone therapy (HT) on cognition in postmenopausal women with Alzheimer's disease (AD) is inconclusive mainly due to a translational gap based on inadequate animal models, clinical inter-/intra-group heterogeneity and often incomparable HT study design.• Cognitive outcomes in clinical trials are mostly influenced by HT composition, its dose, timing and route of administration, as well as by ApoE carrier status, co-morbidity and concomitant therapy.•Design of estrogen/progesterone modulators that would optimize cognitive benefits and tailored HT may lead to more successful prevention and treatment of AD in postmenopausal women.

show abstract

“…They share a number of common features among which are important impact on quality of life and substantial health care costs. Epidemiological and biological evidence support a pathophysiological link between Type 2 Diabetes Mellitus (DMT2) and cognitive impairment [1][2][3]. A causative association between DM and Alzheimer's disease has been suggested on the basis of clinical, epidemiological, genetic and experimental studies [2,[4][5][6][7][8][9].…”

Section: Dmt2: Type 2 Diabetes Mellitus; Mci: Mild Cognitive Impairmentmentioning

confidence: 99%

The Diabetic Brain and Dementia

Jellinger¹

2015

J Alzheimers Dis Parkinsonism

View full text Add to dashboard Cite

Alzheimer's Disease (AD) and Diabetes Mellitus (DM) are the two most common and devastating health problems in the elderly. They share a number of common features among which are important impact on quality of life and substantial health care costs. Epidemiological and biological evidence support a pathophysiological link between Type 2 Diabetes Mellitus (DMT2) and cognitive impairment [1][2][3]. A causative association between DM and Alzheimer's disease has been suggested on the basis of clinical, epidemiological, genetic and experimental studies [2,[4][5][6][7][8][9]. Persons with DM have a higher incidence of cognitive decline and an increased risk of developing AD and other types of dementia, and comorbidity increases the risk [10,11]. Insulin resistance predicts medial temporal hypermetabolism in Mild Cognitive Impairment (MCI) conversion to AD [12] and glucose uptake changes in AD in medial temporal regions predicting worse memory performance [13]. DM has been shown to influence the rate of functional decline among patients with mild AD dementia than in those without comorbid DM [14]. However, the precise mechanisms involved in the development of AD in diabetics are not yet fully understood, and several pathogenic pathways have been discussed [3,4,[15][16][17][18][19][20].Autopsy studies stated that diabetic patients show significantly less AD pathology (senile plaques, neurofibrillary tangles, cerebral amyloid angiopathy, etc.) but more cerebrovascular lesions including microvascular lesions and white matter changes than subjects without DM [5,[21][22][23][24][25][26][27]. Vasculo-neural dysfunction has been suggested to represent a potential etiological linkage between DMT2 and AD [6,28], while others suggested that the association between DM and dementia is only partially mediated through cerebrovascular disease and that DM is associated independently with overal dementia among elderly, but not with AD or vascular dementia [29].Positive DMT2 status appears to exacerbate AD pathology in the presence of ApoE ε4 [30]. Although insulin mitigates Aβ deposition and hyperphosphorylation of tau [17,31], DM in combination with ApoE ε4 may lead to excessive phosphorylation of tau [32], but only in subjects with late stage AD [21]. DM modifies metabolism of Aβ and tau causing Aβ/tau-dependent pathological changes, although there is evidence that suggests an interaction of Aβ/tau-dependent and -independent mechanisms [31]. Evidence supports insulin's role in cognition, synaptic remodelling and facilitation of memory [33]. On the other hand, insulin has been shown to modulate the level of Aβ, to protect neurons against detrimental effects of Aβ on synapses [33]. It further facilitates reduction of amyloid plaques, downregulation of Aβ-derived diffusible ligand-binding sites and also to promote tau hypophosphorylation, which stabilizes microtubules. These data and the observation that the combination of insulin and other antidiabetic medication is associated with lower neuritic plaque density [23,34] are providing a...

show abstract

Type 2 diabetes mellitus and Alzheimer’s disease

Cited by 217 publications

References 34 publications

Inhibitory Activities of Antioxidant Flavonoids from <i>Tamarix gallica</i> on Amyloid Aggregation Related to Alzheimer’s and Type 2 Diabetes Diseases

Inhibitory Activities of Antioxidant Flavonoids from <i>Tamarix gallica</i> on Amyloid Aggregation Related to Alzheimer’s and Type 2 Diabetes Diseases

Evaluating the Role of Hormone Therapy in Postmenopausal Women with Alzheimer’s Disease

The Diabetic Brain and Dementia

Contact Info

Product

Resources

About