Elevated plasma sulfides are associated with cognitive dysfunction and brain atrophy in human Alzheimer's disease and related dementias

Reekes, Tyler; Ledbetter, Christina; Pardue, Sibile; Alexander, J. Steven; Stokes, Karen Y.; Bhuiyan, Mohammad Alfrad Nobel; Patterson, James C.; Lofton, Katelyn T.; Kevil, Christopher G.; Disbrow, Elizabeth A.

doi:10.1016/j.redox.2023.102633

Cited by 9 publications

(5 citation statements)

References 137 publications

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“…A reduction in VEGF has been reported as a risk factor in mouse models of ALS and in humans [ 28 ]. Recently, elevated plasma levels of sulfides have been associated with cognitive disfunction in Alzheimer’s disease and related dementias (ADRDs), and the current authors have proposed H 2 S as a potential vascular biomarker in ADRDs [ 29 , 30 ]. However, other studies have reported a dysregulation of the reverse trans-sulfuration pathway and sulfhydration in Alzheimer’s disease (AD) and a beneficial effect of H 2 S donors on the AD mouse model 3xTg-AD [ 31 ].…”

Section: Hydrogen Sulfide the Vasculature And The Tripartite Synapsementioning

confidence: 99%

The Ying and Yang of Hydrogen Sulfide as a Paracrine/Autocrine Agent in Neurodegeneration: Focus on Amyotrophic Lateral Sclerosis

Spalloni

Stefano

Gimenez

et al. 2023

Cells

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Ever since its presence was reported in the brain, the nature and role of hydrogen sulfide (H2S) in the Central Nervous System (CNS) have changed. Consequently, H2S has been elected as the third gas transmitter, along with carbon monoxide and nitric oxide, and a number of studies have focused on its neuromodulatory and protectant functions in physiological conditions. The research on H2S has highlighted its many facets in the periphery and in the CNS, and its role as a double-faced compound, switching from protective to toxic depending on its concentration. In this review, we will focus on the bell-shaped nature of H2S as an angiogenic factor and as a molecule released by glial cells (mainly astrocytes) and non-neuronal cells acting on the surrounding environment (paracrine) or on the releasing cells themselves (autocrine). Finally, we will discuss its role in Amyotrophic Lateral Sclerosis, a paradigm of a neurodegenerative disease.

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Section: Hydrogen Sulfide the Vasculature And The Tripartite Synapsementioning

confidence: 99%

The Ying and Yang of Hydrogen Sulfide as a Paracrine/Autocrine Agent in Neurodegeneration: Focus on Amyotrophic Lateral Sclerosis

Spalloni

Stefano

Gimenez

et al. 2023

Cells

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“…The emergent "vascular dysregulation hypothesis" postulates a consequential disequilibrium between cerebral perfusion and the metabolic exigencies of neural tissue, thereby amplifying vulnerability to a panoply of AD-associated risk factors. These encompass hypertension, underlying cerebrovascular pathologies, and lifestyle determinants such as physical inactivity [12]. Vascular aberrations endemic to AD have garnered considerable academic scrutiny, with a particular focus on how H 2 S dysregulation engenders vascular irregularities like endothelial dysfunction and diminished cerebral blood flow-variables that exhibit a consistent correlative relationship with AD severity [51][52][53].…”

Section: Dysregulation Of H 2 S Metabolism and Vascular Pathology In Admentioning

confidence: 99%

“…An analytical review of the extant data implicates H 2 S as a significant factor in the correlation between cognitive dysfunction and white matter lesions [12], a salient marker of microvascular pathology [68]. Classifier analyses underscore the diagnostic utility of total plasma sulfide burden as an accurate discriminator between AD and control states [69].…”

Section: The Dialectic Role Of Hydrogen Sulfide In Neurovascular and ...mentioning

confidence: 99%

“…Moreover, one mechanistic pathway through which elevated H 2 S levels may be implicated in AD emerges from the "vascular dysregulation hypothesis", which posits that cerebral hypoxia contributes to AD etiology. Hypoxic and ischemic conditions are known to induce CSE expression, potentially resulting in increased H 2 S biosynthesis under compromised oxygenation, especially in aging brains [12].…”

Section: The Dialectic Role Of Hydrogen Sulfide In Neurovascular and ...mentioning

confidence: 99%

“…Alzheimer's Disease Assessment Scale (ADAS-Cog) is used to quantify cognitive dysfunction [9,10]. Data show a compelling correlation between higher ADAS-Cog scores and elevated levels of H 2 S metabolites in plasma [11,12].…”

Section: Introductionmentioning

confidence: 99%

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Mechanistic Intimate Insights into the Role of Hydrogen Sulfide in Alzheimer’s Disease: A Recent Systematic Review

Munteanu,

Iordan,

Hoteteu

et al. 2023

IJMS

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In the rapidly evolving field of Alzheimer’s Disease (AD) research, the intricate role of Hydrogen Sulfide (H2S) has garnered critical attention for its diverse involvement in both pathological substrates and prospective therapeutic paradigms. While conventional pathophysiological models of AD have primarily emphasized the significance of amyloid-beta (Aβ) deposition and tau protein hyperphosphorylation, this targeted systematic review meticulously aggregates and rigorously appraises seminal contributions from the past year elucidating the complex mechanisms of H2S in AD pathogenesis. Current scholarly literature accentuates H2S’s dual role, delineating its regulatory functions in critical cellular processes—such as neurotransmission, inflammation, and oxidative stress homeostasis—while concurrently highlighting its disruptive impact on quintessential AD biomarkers. Moreover, this review illuminates the nuanced mechanistic intimate interactions of H2S in cerebrovascular and cardiovascular pathology associated with AD, thereby exploring avant-garde therapeutic modalities, including sulfurous mineral water inhalations and mud therapy. By emphasizing the potential for therapeutic modulation of H2S via both donors and inhibitors, this review accentuates the imperative for future research endeavors to deepen our understanding, thereby potentially advancing novel diagnostic and therapeutic strategies in AD.

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Unveiling the negative correlation of formaldehyde and hydrogen sulfide in Parkinson’s disease models using a dual-responsive ruthenium(II) complex probe

Ren,

Zhang,

Gao

et al. 2024

Chemical Engineering Journal

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Elevated plasma sulfides are associated with cognitive dysfunction and brain atrophy in human Alzheimer's disease and related dementias

Cited by 9 publications

References 137 publications

The Ying and Yang of Hydrogen Sulfide as a Paracrine/Autocrine Agent in Neurodegeneration: Focus on Amyotrophic Lateral Sclerosis

The Ying and Yang of Hydrogen Sulfide as a Paracrine/Autocrine Agent in Neurodegeneration: Focus on Amyotrophic Lateral Sclerosis

Mechanistic Intimate Insights into the Role of Hydrogen Sulfide in Alzheimer’s Disease: A Recent Systematic Review

Unveiling the negative correlation of formaldehyde and hydrogen sulfide in Parkinson’s disease models using a dual-responsive ruthenium(II) complex probe

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