Showing posts with label SIRT proteins. Show all posts
Showing posts with label SIRT proteins. Show all posts
Sunday, March 1, 2026
Monday, April 14, 2025
USP7 promotes PINK1/Parkin-dependent mitophagy to ameliorate cerebral ischemia–reperfusion injury by deubiquitinating and stabilizing SIRT1
Sounds important for our recovery. Do you really think your incompetent doctor and hospital will ensure human testing gets done? Competent entities would do that!
USP7 promotes PINK1/Parkin-dependent mitophagy to ameliorate cerebral ischemia–reperfusion injury by deubiquitinating and stabilizing SIRT1
Saturday, September 28, 2024
Neurodegeneration: Effects of calorie restriction on the brain sirtuin protein levels
Does your doctor and stroke hospital have enough functioning neurons to see this and get human testing initiated? NO? So you don't have a functioning stroke doctor or hospital? RUN AWAY!
Neurodegeneration: Effects of calorie restriction on the brain sirtuin protein levels
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Introduction
Neurodegenerative
diseases (NDDs) pose substantial health challenges, causing severe
morbidity and disabilities that can impact a significant portion of the
population [1], [2], [3], [4]. Currently, dementia affects 36.5 million
individuals globally, with 5–7 million new cases of Alzheimer's Disease
(AD) recorded each year [2], [5]. Census data predicts 13.8 million AD
patients in the USA by 2050 [6]. Multiple factors within human
populations affect the impact of disorders and mortality. Giannouli
underscores the critical roles that family bonds and
religiosity–spirituality may play in treatment maintenance, adherence,
and outcomes [7]. These elements also enhance disease resistance through
social support, reduced exposure to environmental risk factors, and
improved management of comorbid medical conditions that could lead to
death. However, limited information in medical records and challenges in
conducting new prospective studies pose significant restrictions.
Sirtuin
Proteins (SIRT) constitute a crucial group of proteins involved in gene
silencing, genomic stability, cellular longevity, and metabolic
regulation through the deacetylation of histones. Comprising seven
well-conserved protein complexes, sirtuins play a vital role in aging,
apoptosis, and neurodegenerative diseases by regulating cellular
stability [8], [9], [10]. They are instrumental in remodeling chromatin,
influencing cellular mechanisms, and modulating gene expression.
Numerous studies, employing various animal models, have underscored the
involvement of SIRT in neurological diseases [8], [11], [12], [13],
[14], [15], [16].
In this
context, research has demonstrated that overexpression of SIRT1
protects neurons from toxicity induced by mutated superoxide dismutase 1
in both neuron cultures and mouse brains [17], [18]. Conversely,
deficiencies in SIRT have been shown to exacerbate neurodegenerative
disorders in lethal neurological diseases [19]. SIRT1 and SIRT3 emerge
as key players in neuronal functions, particularly influencing synaptic
plasticity and memory formation [20]. Their regulatory roles in the
brain's essential functions position them as potential contributors to
the pathogenesis of various neurodegenerative disorders [21].
The
significance of both SIRT1 and SIRT6 stems from their regulatory
effects on NF-κB. NF-κB governs genes involved in apoptosis, cell aging,
inflammation, and immunity, with its activity increasing with age in
many mammalian tissues and stem cells [22]. In the central nervous
system, microglia and astrocytes influence inflammation and
neurodegeneration. While microglia regulate pro-inflammatory and
neurotoxic activities in astrocytes, the precise mechanisms remain
unclear. Recent findings suggest that microglia-produced TGFα plays a
role in modulating the pathogenic activities of astrocytes in
experimental models of NDD [23].
To
ascertain the precise involvement of TGF-α in glial activation
following traumatic brain injury, Isuno et al. explored the responses of
astroglial and microglial cells in MMTV-TGF-α positive mice with TGF-α
overexpression induced by a cortical injury. The findings suggested that
TGF-α overexpression has a potential role in influencing neuronal
function [24]. TGFα regulate NF-κB pathogenic activities during CNS
inflammation and it is involved in, neuroprotection, astrogliosis and
prevention of NDD [25].
SIRT6
plays essential roles in the pathophysiology of Alzheimer's disease
(AD), participating in telomere preservation, DNA repair, genome
integrity, energy metabolism, and inflammation factors that collectively
influence lifespan [26]. Recent research indicating the absence of
SIRT6 in AD patients suggests its potential as a novel therapeutic
target in the treatment of AD [26].
Calorie
restriction (CR) involves reducing calorie intake without causing
nutritional deficiencies [8], [9], [10]. Studies in laboratory rodents
have shown that a 30–40 % reduction in ad libitum (AL) food intake can
extend lifespan by 50 % [11]. Two common CR protocols, chronic calorie
restriction (CCR) and intermittent calorie restriction (ICR), are
believed to activate protective mechanisms against neurodegeneration
(ND) and age-related diseases [15], [16]. Despite existing literature
highlighting the protective role of SIRT proteins against age-related
ND, no study has explored the total levels of SIRT 1, 3, and 6 proteins
simultaneously in brain homogenates by ELISA following intermittent
calorie restriction.
In
this study, we hypothesized that "CR modulates SIRT protein levels, and
the type of calorie consumption regulates ND." Applying CCR or ICR
protocols in mice to induce stress[3], [10], [12], [16], [19], [20], we
aimed to determine whether ND would be more pronounced with AL or with
CR.
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Sunday, May 5, 2024
Nicotinamide riboside attenuates myocardial ischemia-reperfusion injury via regulating SIRT3/SOD2 signaling pathway
Hopefully your competent? doctor is fully aware of what this can do.
Nicotinamide riboside attenuates myocardial ischemia-reperfusion injury via regulating SIRT3/SOD2 signaling pathway
Under a Creative Commons license
open access
Graphical Abstract
Our findings demonstrate that pretreatment with NR significantly reduces myocardial infarct area, decreases levels of CK-MB and LDH in serum, and improves cardiac function in the rats during myocardial ischemia-reperfusion (I/R) injury. Meanwhile, NR also effectively increases the viability and decreases the LDH release of H9c2 cells during OGD/R. Mechanically, we have provided evidence that NR pretreatment could decrease mitochondrial reactive oxygen species (mtROS) production and MDA content, and enhance SOD activity, thereby mitigating mitochondrial damage and inhibiting apoptosis during myocardial I/R injury. Further investigations revealed that NR increased NAD+ content and upregulated SIRT3 protein expression in myocardium. Through using of SIRT3 small interfering RNA and the SIRT3 deacetylase activity inhibitor 3-TYP, we have confirmed that the cardioprotective effect of NR on cardiomyocytes was largely dependent on the inhibition of mitochondrial oxidative stress via SIRT3-SOD2 axis. Overall, our comprehensive exploration into the mechanisms underlying NR-mediated myocardial protection will provide a theoretical foundation for prevention and therapy on myocardial I/R injury.
More at link.
Monday, February 21, 2022
Resveratrol Preconditioning Induces a Novel Extended Window of Ischemic Tolerance in the Mouse Brain
You'll have to ask your doctor how many bottles of red wine you need to consume daily to get this beneficial effect, accounting for the increase in body size from mouse to human.
Resveratrol Preconditioning Induces a Novel Extended Window of Ischemic Tolerance in the Mouse Brain
Kevin B. Koronowski, BS; Kunjan R. Dave, PhD; Isabel Saul, BS; Vladimir Camarena, PhD;
John W. Thompson, PhD; Jake T. Neumann, PhD; Juan I. Young, PhD; Miguel A. Perez-Pinzon, PhD
John W. Thompson, PhD; Jake T. Neumann, PhD; Juan I. Young, PhD; Miguel A. Perez-Pinzon, PhD
Background and Purpose—
Prophylactic treatments that afford neuroprotection against stroke may emerge from the field of preconditioning. Resveratrol mimics ischemic preconditioning, reducing ischemic brain injury when administered 2 days before global ischemia in rats. This protection is linked to silent information regulator 2 homologue 1 (Sirt1) and enhanced mitochondrial function possibly through its repression of uncoupling protein 2. Brain-derived neurotrophic factor (BDNF) is another neuroprotective protein associated with Sirt1. In this study, we sought to identify the conditions of resveratrol preconditioning (RPC) that most robustly induce neuroprotection against focal ischemia in mice.
Methods—
We tested 4 different RPC paradigms against a middle cerebral artery occlusion model of stroke. Infarct volume and neurological score were calculated 24 hours after middle cerebral artery occlusion. Sirt1-chromatin binding was evaluated by ChIP-qPCR. Percoll gradients were used to isolate synaptic fractions, and changes in protein expression were determined via Western blot analysis. BDNF concentration was measured using a BDNF-specific ELISA assay.
Results—
Although repetitive RPC induced neuroprotection from middle cerebral artery occlusion, strikingly one application of RPC 14 days before middle cerebral artery occlusion showed the most robust protection, reducing infarct volume by 33% and improving neurological score by 28%. Fourteen days after RPC, Sirt1 protein was increased 1.5-fold and differentially bound to the uncoupling protein 2 and BDNF promoter regions. Accordingly, synaptic uncoupling protein 2 level decreased by 23% and cortical BDNF concentration increased 26%.
Conclusions—
RPC induces a novel extended window of ischemic tolerance in the brain that lasts for at least 14 days.
Our data suggest that this tolerance may be mediated by Sirt1 through upregulation of BDNF and downregulation of
uncoupling protein 2. (Stroke. 2015;46:2293-2298. DOI: 10.1161/STROKEAHA.115.009876.)
Key Words: BDNF ◼ cerebral ischemia ◼ preconditioning ◼ resveratrol ◼ UCP2
Our data suggest that this tolerance may be mediated by Sirt1 through upregulation of BDNF and downregulation of
uncoupling protein 2. (Stroke. 2015;46:2293-2298. DOI: 10.1161/STROKEAHA.115.009876.)
Key Words: BDNF ◼ cerebral ischemia ◼ preconditioning ◼ resveratrol ◼ UCP2
Tuesday, March 23, 2021
Abstract P806: Sirtuin1 Plays a Critical Role in Reversing Skeletal Muscle Atrophy in Cerebral Ischemic Stroke
But is solving sirtuin-2 better than sirtuin-1? Did your stroke hospital do ONE DAMN THING to get human research done for sirtuin-2?
Knockout of Silent Information Regulator 2 (SIRT2) Preserves Neurological Function after Experimental Stroke in Mice October 2017
The latest here:
Abstract P806: Sirtuin1 Plays a Critical Role in Reversing Skeletal Muscle Atrophy in Cerebral Ischemic Stroke
Abstract
Stroke is a leading cause of mortality and long-term disability in patients worldwide. Skeletal muscle is the primary systemic target organ of stroke that severely induces muscle wasting and weakness, which contributes more to the long-term functional disability in stroke patients than any other disease. Currently, no approved pharmacological drug is available to treat stroke-induced muscle loss. Rehabilitative therapy is the only available option to improve muscle function in stroke patients. However, higher muscle fatigability and lower muscle strength from extensive muscle wasting in post-stroke patients provide poor rehabilitative outcomes. As a result, about two-thirds of stroke survivors persist in a state of insufficient recovery and experience physical disability that drastically reduces their health and quality of life. The major challenge in the drug discovery effort for treating post-stroke muscle wasting is the lack of our understanding of the molecular and/or cellular mechanisms that underlie the muscle wasting in stroke. To understand the molecular origin of stroke-induced muscle atrophy, gene expression profiling and associated biological pathway enrichment studies were performed in a mouse model of cerebral ischemic stroke using high-throughput RNA sequencing and extensive bioinformatic analyses. RNA-seq data revealed that the elevated atrophy in skeletal muscle observed in response to stroke was primairly associated with the altered expression of genes involved in the muscle protein degradation pathway. Further analysis of RNA-seq data identified Sirtuin1 (SirT1) as a critical protein that plays a significant role in regulating post-stroke muscle mass. SirT1 gain-of-function in skeletal muscle significantly reversed stroke-induced muscle atrophy via inhibiting the activation of the ubiquitin proteasomal pathway and restoring autophagy function. Collectively, this study identified suppression of SirT1as a novel mechanism by which stroke induces muscle atrophy.
Thursday, May 28, 2020
Muscle‐specific sirtuin1 gain‐of‐function ameliorates skeletal muscle atrophy in a pre‐clinical mouse model of cerebral ischemic stroke
And since resveratrol stimulates production of SIRT1, a serum that blocks diseases by speeding up the cell's energy production centers known as mitrochondria. Ask your doctor how much red wine you should be drinking to prevent such atrophy. Until we know a better way on this red wine is the obvious choice. I bet your stroke hospital will never serve red wine.
The latest here:
Muscle‐specific sirtuin1 gain‐of‐function ameliorates skeletal muscle atrophy in a pre‐clinical mouse model of cerebral ischemic stroke
First published: 21 May 2020
This article has been accepted for publication and
undergone full peer review but has not been through the copyediting,
typesetting, pagination and proofreading process, which may lead to
differences between this version and the Version of Record. Please cite
this article as doi:10.1096/fba.2020‐00017
Abstract
Stroke causes severe long‐term disability in patients due to
the induction of skeletal muscle atrophy and weakness, but the
molecular mechanisms remain elusive. Using a preclinical mouse model of
cerebral ischemic stroke, we show that stroke robustly induced atrophy
as well as significantly decreased gene expression in the PTA
(paralytic tibialis anterior) muscle. Muscle‐specific SirT1
gain‐of‐function mice are resistant to stroke‐induced muscle atrophy and
this protective effect requires its deacetylase activity. Although
SirT1 counteracts the stroke‐induced up‐regulation of atrogin1, MuRF1
and ZNF216 genes, we found a mechanism that regulates the ZNF216 gene
transcription in post‐stroke muscle. Stroke increased the expression of
the ZNF216 gene in post‐stroke TA muscle by activating PARP‐1, which
binds on the ZNF216 promoter. The SirT1 gain‐of‐function or SirT1
activator, resveratrol, reversed the PARP‐1‐mediated up‐regulation of
ZNF216 expression at the promoter level, suggesting a contradicted role
for SirT1 and PARP‐1 in the regulation of ZNF216 gene. Overall, our
study for the first‐time demonstrated that (1) stroke causes muscle
atrophy, in part, through the SirT1/PARP‐1/ZNF216 signaling mechanism,
(2) SirT1 can block muscle atrophy in response to different types of
atrophic signals via different signaling mechanisms, and (3) identified SirT1 as a critical regulator of post‐stroke muscle mass.
Sunday, June 2, 2019
Resveratrol and cardiovascular health
Useless, just bland statements. I want to know EXACTLY how much red wine to drink on a daily basis or some similar replacement. We can't wait forever for those resveratrol tomatoes.
Resveratrol and cardiovascular health
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