Early Biomarkers of Neurodegenerative and Neurovascular Disorders in Diabetes

Siwik, Dominika; Gajewska, Magdalena; Jaguszewski, Miłosz; Mazurek, Tomasz; Postuła, Marek; Eyileten, Ceren

doi:10.3390/jcm9092807

Cited by 59 publications

(41 citation statements)

References 118 publications

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“…In the course of inflammation, acute-phase proteins, including C-reactive protein (CRP) are produced in response to cytokine stimulation. Under physiological conditions, the level of CRP synthesis is low, however, the production increases in inflammation and it is observed in many inflammatory diseases, including diabetes [ 27 , 28 , 29 ]. Previous studies have demonstrated the elevated blood levels of CRP in patients with T1DM and T2DM suffering from diabetic complications, such as diabetic retinopathy (DR) [ 18 , 24 , 25 , 26 , 27 ].…”

Section: The Retina—hyperglycaemia and Inflammation In The Course mentioning

confidence: 99%

“…In other studies, the authors attempted to demonstrate whether selected inflammatory proteins may be associated with microvascular complications in adult T1DM patients [ 29 ]. In a group of 100 subjects with T1DM, the following parameters were determined: epidermal growth factor (EGF), metalloproteinase 2 (MMP-2), growth/differentiation factor 15 (GDF-15) and interleukin 29 (IL-29).…”

Section: The Retina—hyperglycaemia and Inflammation In The Course mentioning

confidence: 99%

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Retinal Vascular Endothelial Cell Dysfunction and Neuroretinal Degeneration in Diabetic Patients

Mrugacz

Bryl

Zorena

2021

JCM

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Diabetes mellitus (DM) has become a vital societal problem as epidemiological studies demonstrate the increasing incidence of type 1 and type 2 diabetes. Lesions observed in the retina in the course of diabetes, referred to as diabetic retinopathy (DR), are caused by vascular abnormalities and are ischemic in nature. Vascular lesions in diabetes pertain to small vessels (microangiopathy) and involve precapillary arterioles, capillaries and small veins. Pericyte loss, thickening of the basement membrane, and damage and proliferation of endothelial cells are observed. Endothelial cells (monolayer squamous epithelium) form the smooth internal vascular lining indispensable for normal blood flow. Breaking its continuity initiates blood coagulation at that site. The endothelium controls the process of exchange of chemical substances (nutritional, regulatory, waste products) between blood and the retina, and blood cell passing through the vascular wall. Endothelial cells produce biologically active substances involved in blood coagulation, regulating vascular wall tension and stimulating neoangiogenesis. On the other hand, recent studies have demonstrated that diabetic retinopathy may be not only a microvascular disease, but is a result of neuroretinal degeneration. Neuroretinal degeneration appears structurally, as neural apoptosis of amacrine and Muller cells, reactive gliosis, ganglion cell layer/inner plexiform (GCL) thickness, retinal thickness, and retinal nerve fiber layer thickness, and a reduction of the neuroretinal rim in minimum rim width (MRW) and functionally as an abnormal electroretinogram (ERG), dark adaptation, contrast sensitivity, color vision, and microperimetric test. The findings in early stages of diabetic retinopathy may precede microvascular changes of this disease. Furthermore, the article’s objective is to characterize the factors and mechanisms conducive to microvascular changes and neuroretinal apoptosis in diabetic retinopathy. Only when all the measures preventing vascular dysfunction are determined will the risk of complications in the course of diabetes be minimized.

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Section: The Retina—hyperglycaemia and Inflammation In The Course mentioning

confidence: 99%

Section: The Retina—hyperglycaemia and Inflammation In The Course mentioning

confidence: 99%

Retinal Vascular Endothelial Cell Dysfunction and Neuroretinal Degeneration in Diabetic Patients

Mrugacz

Bryl

Zorena

2021

JCM

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“…Examining the neuropathological records from an autopsy series, there was no significant correlation between type-2 diabetes and the severity of plaque and tangle load in brain regions affected by AD [ 136 ], with the exception of subjects with an apolipoprotein E4 allele. It was confirmed in a more recent study that type-2 diabetes did not correlate with the amyloid plaque or neurofibrillary tangle load, but it was commented on that both diseases are associated at early stages with a significant cerebrovascular disease that can affect the development of AD pathology [ 27 ]. Much interest in this topic has been on whether patients treated with the insulin sensitizer metformin have a reduced risk of dementia [ 137 , 138 , 139 ].…”

Section: Txnip Expression In the Brainmentioning

confidence: 99%

“…TXNIP might be an important hub coordinator of different pathological processes in this disease, but there has been only one published study on its expression and distribution in human AD brains, and further studies are needed [ 26 ]. We will also consider the evidence for the pathological contribution of diabetes and diabetes-induced oxidative stress to Alzheimer’s disease (AD) as part of this review [ 27 ], and how it can be linked to TXNIP.…”

Section: Introductionmentioning

confidence: 99%

Thioredoxin-Interacting Protein (TXNIP) with Focus on Brain and Neurodegenerative Diseases

Tsubaki

Tooyama

Walker

2020

IJMS

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The development of new therapeutic approaches to diseases relies on the identification of key molecular targets involved in amplifying disease processes. One such molecule is thioredoxin-interacting protein (TXNIP), also designated thioredoxin-binding protein-2 (TBP-2), a member of the α-arrestin family of proteins and a central regulator of glucose and lipid metabolism, involved in diabetes-associated vascular endothelial dysfunction and inflammation. TXNIP sequesters reduced thioredoxin (TRX), inhibiting its function, resulting in increased oxidative stress. Many different cellular stress factors regulate TXNIP expression, including high glucose, endoplasmic reticulum stress, free radicals, hypoxia, nitric oxide, insulin, and adenosine-containing molecules. TXNIP is also directly involved in inflammatory activation through its interaction with the nucleotide-binding domain, leucine-rich-containing family, and pyrin domain-containing-3 (NLRP3) inflammasome complex. Neurodegenerative diseases such as Alzheimer’s disease have significant pathologies associated with increased oxidative stress, inflammation, and vascular dysfunctions. In addition, as dysfunctions in glucose and cellular metabolism have been associated with such brain diseases, a role for TXNIP in neurodegeneration has actively been investigated. In this review, we will focus on the current state of the understanding of possible normal and pathological functions of TXNIP in the central nervous system from studies of in vitro neural cells and the brains of humans and experimental animals with reference to other studies. As TXNIP can be expressed by neurons, microglia, astrocytes, and endothelial cells, a complex pattern of regulation and function in the brain is suggested. We will examine data suggesting TXNIP as a therapeutic target for neurodegenerative diseases where further research is needed.

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“…In addition to biomarkers localized in intracellular organelles or specific cells, this review focuses on systemic biomarkers, such as serum, which are less invasive and can be easily quantified. Other excellent reviews [ 7 , 8 , 9 ] also describe local biomarkers. In addition, since biomarkers are molecules whose levels fluctuate during disease progression, they are often the cause on their own; hence, supplementing them can slow down or restore the progress of disease.…”

Section: Introductionmentioning

confidence: 99%

Recent Advances in Biomarkers and Regenerative Medicine for Diabetic Neuropathy

Fujita

Murakami

Nakamura

2021

IJMS

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Diabetic neuropathy is one of the most common complications of diabetes. This complication is peripheral neuropathy with predominant sensory impairment, and its symptoms begin with hyperesthesia and pain and gradually become hypoesthesia with the loss of nerve fibers. In some cases, lower limb amputation occurs when hypoalgesia makes it impossible to be aware of trauma or mechanical stimuli. On the other hand, up to 50% of these complications are asymptomatic and tend to delay early detection. Therefore, sensitive and reliable biomarkers for diabetic neuropathy are needed for an early diagnosis of this condition. This review focuses on systemic biomarkers that may be useful at this time. It also describes research on the relationship between target gene polymorphisms and pathological conditions. Finally, we also introduce current information on regenerative therapy, which is expected to be a therapeutic approach when the pathological condition has progressed and nerve degeneration has been completed.

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Early Biomarkers of Neurodegenerative and Neurovascular Disorders in Diabetes

Cited by 59 publications

References 118 publications

Retinal Vascular Endothelial Cell Dysfunction and Neuroretinal Degeneration in Diabetic Patients

Retinal Vascular Endothelial Cell Dysfunction and Neuroretinal Degeneration in Diabetic Patients

Thioredoxin-Interacting Protein (TXNIP) with Focus on Brain and Neurodegenerative Diseases

Recent Advances in Biomarkers and Regenerative Medicine for Diabetic Neuropathy

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