A possible role of glycation in the regulation of amyloid β precursor protein processing leading to amyloid β accumulation

Patil, Gouri V.; Joshi, Rakesh S.; Kazi, Rubina; Kulsange, Shabda E; Kulkarni, Mahesh J.

doi:10.1016/j.mehy.2020.109799

Cited by 8 publications

(2 citation statements)

References 57 publications

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“…Additionally, elevated glucose levels influence the production and degradation of Aβ ( Macauley et al, 2015 ; Kubis-Kubiak et al, 2019 ). There is evidence indicating that certain Aβ products undergo predominant degradation through the proteasome pathway, which is significantly destabilized by increased glucose levels ( Kubis-Kubiak et al, 2019 ; Patil et al, 2020 ). Nonetheless, different regions seem to have specific vulnerabilities and different mechanisms might underly atrophy in particular regions.…”

Section: Discussionmentioning

confidence: 99%

Irreversible atrophy in memory brain regions over 7 years is predicted by glycemic control in type 2 diabetes without mild cognitive impairment

Canário,

Crisóstomo,

Duarte

et al. 2024

Front. Aging Neurosci.

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Memory-related impairments in type 2 diabetes may be mediated by insulin resistance and hyperglycemia. Previous cross-sectional studies have controversially suggested a relationship between metabolic control and a decrease in hippocampal volumes, but only longitudinal studies can test this hypothesis directly. We performed a longitudinal morphometric study to provide a direct test of a possible role of higher levels of glycated hemoglobin with long term brain structural integrity in key regions of the memory system – hippocampus, parahippocampal gyrus and fusiform gyrus. Grey matter volume was measured at two different times – baseline and after ~7 years. We found an association between higher initial levels of HbA1C and grey matter volume loss in all three core memory regions, even in the absence of mild cognitive impairment. Importantly, these neural effects persisted in spite of the fact that patients had significantly improved their glycemic control. This suggests that early high levels of HbA1c might be irreversibly associated with subsequent long-term atrophy in the medial temporal cortex and that early intensive management is critical.

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Section: Discussionmentioning

confidence: 99%

Irreversible atrophy in memory brain regions over 7 years is predicted by glycemic control in type 2 diabetes without mild cognitive impairment

Canário,

Crisóstomo,

Duarte

et al. 2024

Front. Aging Neurosci.

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“…Alterations in these enzymes during the early stages of AD have been reported as crucial to disease progression [ 45 , 47 ]. Glycation reactions are suggested to enhance Aβ formation pathways in amyloid precursor protein (APP) processing mechanisms [ 73 ], and the clearance of Aβ by astrocytes was impaired after inhibiting insulin signaling pathways, in turn reducing NEP and IDE levels [ 74 ]. Despite that, the alterations in glycation induced by MG in our conditions did not impact these targets involved in the Aβ metabolism.…”

Section: Discussionmentioning

confidence: 99%

In Vitro Astroglial Dysfunction Induced by Neurotoxins: Mimicking Astrocytic Metabolic Alterations of Alzheimer’s Disease

Taday,

Fróes,

Seady

et al. 2024

Metabolites

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Astrocytes play fundamental roles in the maintenance of brain homeostasis. The dysfunction of these cells is widely associated with brain disorders, which are often characterized by variations in the astrocyte protein markers GFAP and S100B, in addition to alterations in some of its metabolic functions. To understand the role of astrocytes in neurodegeneration mechanisms, we induced some of these metabolic alterations, such as energy metabolism, using methylglyoxal (MG) or fluorocitrate (FC); and neuroinflammation, using lipopolysaccharide (LPS) and streptozotocin (STZ), which is used for inducing Alzheimer’s disease (AD) in animal models. We showed that MG, LPS, STZ and FC similarly caused astrocyte dysfunction by increasing GFAP and reducing S100B secretion. In the context of AD, STZ caused an amyloid metabolism impairment verified by increases in Aβ1-40 peptide content and decreases in the amyloid degradation enzymes, IDE and NEP. Our data contribute to the understanding of the role of astrocytes in brain injury mechanisms and suggest that STZ is suitable for use in vitro models for studying the role of astrocytes in AD.

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The Involvement of Post-Translational Modifications in Regulating the Development and Progression of Alzheimer’s Disease

Guan

Wang

2023

Mol Neurobiol

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A possible role of glycation in the regulation of amyloid β precursor protein processing leading to amyloid β accumulation

Cited by 8 publications

References 57 publications

Irreversible atrophy in memory brain regions over 7 years is predicted by glycemic control in type 2 diabetes without mild cognitive impairment

Irreversible atrophy in memory brain regions over 7 years is predicted by glycemic control in type 2 diabetes without mild cognitive impairment

In Vitro Astroglial Dysfunction Induced by Neurotoxins: Mimicking Astrocytic Metabolic Alterations of Alzheimer’s Disease

The Involvement of Post-Translational Modifications in Regulating the Development and Progression of Alzheimer’s Disease

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