scholarly journals Understanding the Potential Role of Sirtuin 2 on Aging: Consequences of SIRT2.3 Overexpression in Senescence

2021 ◽  
Vol 22 (6) ◽  
pp. 3107
Author(s):  
Noemi Sola-Sevilla ◽  
Ana Ricobaraza ◽  
Ruben Hernandez-Alcoceba ◽  
Maria S. Aymerich ◽  
Rosa M. Tordera ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Potential Role ◽  
Adeno Associated Virus ◽  
Age Related ◽  
Age Dependent ◽  
Molecular Effects ◽  
Samp8 Mice ◽  
The Brain

Sirtuin 2 (SIRT2) has been associated to aging and age-related pathologies. Specifically, an age-dependent accumulation of isoform 3 of SIRT2 in the CNS has been demonstrated; however, no study has addressed the behavioral or molecular consequences that this could have on aging. In the present study, we have designed an adeno-associated virus vector (AAV-CAG-Sirt2.3-eGFP) for the overexpression of SIRT2.3 in the hippocampus of 2 month-old SAMR1 and SAMP8 mice. Our results show that the specific overexpression of this isoform does not induce significant behavioral or molecular effects at short or long term in the control strain. Only a tendency towards a worsening in the performance in acquisition phase of the Morris Water Maze was found in SAMP8 mice, together with a significant increase in the pro-inflammatory cytokine Il-1β. These results suggest that the age-related increase of SIRT2.3 found in the brain is not responsible for induction or prevention of senescence. Nevertheless, in combination with other risk factors, it could contribute to the progression of age-related processes. Understanding the specific role of SIRT2 on aging and the underlying molecular mechanisms is essential to design new and more successful therapies for the treatment of age-related diseases.

Potential Role of Adult Hippocampal Neurogenesis in Traumatic Brain Injury

2021 ◽  
Vol 28 ◽  
Author(s):  
Lucas Alexandre Santos Marzano ◽  
Fabyolla Lúcia Macedo de Castro ◽  
Caroline Amaral Machado ◽  
João Luís Vieira Monteiro de Barros ◽  
Thiago Macedo e Cordeiro ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Clinical Studies ◽  
Molecular Mechanisms ◽  
Hippocampal Neurogenesis ◽  
Cognitive Outcomes ◽  
Adult Hippocampal Neurogenesis ◽  
The Brain

: Traumatic brain injury (TBI) is a serious cause of disability and death among young and adult individuals, displaying complex pathophysiology including cellular and molecular mechanisms that are not fully elucidated. Many experimental and clinical studies investigated the potential relationship between TBI and the process by which neurons are formed in the brain, known as neurogenesis. Currently, there are no available treatments for TBI’s long-term consequences being the search for novel therapeutic targets, a goal of highest scientific and clinical priority. Some studies evaluated the benefits of treatments aimed at improving neurogenesis in TBI. In this scenario, herein, we reviewed current pre-clinical studies that evaluated different approaches to improving neurogenesis after TBI while achieving better cognitive outcomes, which may consist in interesting approaches for future treatments.

scholarly journals Neuroinflammation and Its Impact on the Pathogenesis of COVID-19

2021 ◽  
Vol 8 ◽  
Author(s):  
Mohammed M. Almutairi ◽  
Farzane Sivandzade ◽  
Thamer H. Albekairi ◽  
Faleh Alqahtani ◽  
Luca Cucullo
Keyword(s):  
Immune System ◽  
Molecular Mechanisms ◽  
Potential Role ◽  
Immune Cell ◽  
Clinical Manifestations ◽  
Cell Infiltration ◽  
Cellular Mechanisms ◽  
Cytokine Levels

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The clinical manifestations of COVID-19 include dry cough, difficult breathing, fever, fatigue, and may lead to pneumonia and respiratory failure. There are significant gaps in the current understanding of whether SARS-CoV-2 attacks the CNS directly or through activation of the peripheral immune system and immune cell infiltration. Although the modality of neurological impairments associated with COVID-19 has not been thoroughly investigated, the latest studies have observed that SARS-CoV-2 induces neuroinflammation and may have severe long-term consequences. Here we review the literature on possible cellular and molecular mechanisms of SARS-CoV-2 induced-neuroinflammation. Activation of the innate immune system is associated with increased cytokine levels, chemokines, and free radicals in the SARS-CoV-2-induced pathogenic response at the blood-brain barrier (BBB). BBB disruption allows immune/inflammatory cell infiltration into the CNS activating immune resident cells (such as microglia and astrocytes). This review highlights the molecular and cellular mechanisms involved in COVID-19-induced neuroinflammation, which may lead to neuronal death. A better understanding of these mechanisms will help gain substantial knowledge about the potential role of SARS-CoV-2 in neurological changes and plan possible therapeutic intervention strategies.

scholarly journals Kynurenic acid and cancer: facts and controversies

2019 ◽  
Vol 77 (8) ◽  
pp. 1531-1550 ◽  
Author(s):  
Katarzyna Walczak ◽  
Artur Wnorowski ◽  
Waldemar A. Turski ◽  
Tomasz Plech
Keyword(s):  
Kynurenic Acid ◽  
Molecular Mechanisms ◽  
Potential Role ◽  
Cancer Cell Proliferation ◽  
Gastrointestinal Microbiota ◽  
Tryptophan Metabolite ◽  
Peripheral Cells ◽  
The Relationship ◽  
The Brain

Abstract Kynurenic acid (KYNA) is an endogenous tryptophan metabolite exerting neuroprotective and anticonvulsant properties in the brain. However, its importance on the periphery is still not fully elucidated. KYNA is produced endogenously in various types of peripheral cells, tissues and by gastrointestinal microbiota. Furthermore, it was found in several products of daily human diet and its absorption in the digestive tract was evidenced. More recent studies were focused on the potential role of KYNA in carcinogenesis and cancer therapy; however, the results were ambiguous and the biological activity of KYNA in these processes has not been unequivocally established. This review aims to summarize the current views on the relationship between KYNA and cancer. The differences in KYNA concentration between physiological conditions and cancer, as well as KYNA production by both normal and cancer cells, will be discussed. The review also describes the effect of KYNA on cancer cell proliferation and the known potential molecular mechanisms of this activity.

scholarly journals ROLE OF INSULIN IN BRAIN: DELVE INTO THE MOLECULAR MECHANISMS

2021 ◽  
Author(s):  
Sofia Khanam
Keyword(s):  
Molecular Mechanisms ◽  
Insulin Signalling ◽  
Diabetic Patients ◽  
Functional Activities ◽  
Mitochondrial Alterations ◽  
Age Related ◽  
The Brain ◽  
And Oxidative Stress

We have learned over the last several decades that the brain is an important target for insulin action. In central nervous system (CNS) it mainly affects feeding behaviour and various aspects of memory and cognition. Insulin signalling in CNS has emerged as a novel field of research since decreases brain insulin levels and signalling were associated to impaired learning, memory and age-related neurodegenerative diseases. Alterations of these functional activities may contribute to the manifestation of several clinical entities, such as central insulin resistance, type 2 diabetes mellitus (T2DM) and Alzheimer’s disease (AD). A close alliance between T2DM and AD has been reported, to the extent that AD is twice more frequent in diabetic patients. There are links between T2DM and AD through mitochondrial alterations and oxidative stress, altered energy and glucose metabolism, cholesterol modifications, dysfunctional protein O-GlcNAcylation, formation of amyloid plaques, altered Aβ metabolism and tau hyperphosphorylation. Herewith, we aim to integrate the metabolic, neuromodulatory, and neuroprotective roles of insulin in two age-related pathologies: T2DM and AD, both in terms of intracellular signalling and potential therapeutic approach.

Inflammatory Molecular Mediators and Pathways Involved in Vascular Aging and Stroke: A Comprehensive Review

2021 ◽  
Vol 28 ◽  
Author(s):  
Amro M. Soliman ◽  
Srijit Das ◽  
Pasuk Mahakkanukrauh
Keyword(s):  
Drug Targets ◽  
Molecular Mechanisms ◽  
Potential Role ◽  
Vascular Diseases ◽  
Vascular Aging ◽  
Inflammatory Conditions ◽  
Age Related ◽  
Cardiovascular Pathologies ◽  
Potential Drug Targets

: There is an increase in the incidence of cardiovascular diseases with aging and it is one of the leading causes of death worldwide. The main cardiovascular pathologies include atherosclerosis, stroke, myocardial infarction, hypertension and stroke. Chronic inflammation is one of the significant contributors to the age-related vascular diseases. Therefore, it is important to understand the molecular mechanisms of the persistent inflammatory conditions occurring in the blood vessels as well as the signaling pathways involved. Herein, we performed an extant search of literature involving PubMed, ISI, WoS and Scopus databases for retrieving all relevant articles with the most recent findings illustrating the potential role of various inflammatory mediators along with their proposed activated pathways in the pathogenesis and progression of vascular aging. We also highlight the major pathways contributing to age-related vascular disorders. The outlined molecular mechanisms, pathways and mediators of vascular aging represent potential drug targets that can be utilized to inhibit and/or slow the pathogenesis and progression of vascular aging.

scholarly journals Regular and Moderate Exercise Counteracts the Decline of Antioxidant Protection but Not Methylglyoxal-Dependent Glycative Burden in the Ovary of Reproductively Aging Mice

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
S. Falone ◽  
S. Jr Santini ◽  
V. Cordone ◽  
M. Grannonico ◽  
M. Cacchio ◽  
...  
Keyword(s):  
Healthy Aging ◽  
Molecular Mechanisms ◽  
Population Aging ◽  
Oxygen Species ◽  
Moderate Exercise ◽  
Mouse Ovary ◽  
Age Related ◽  
Age Dependent ◽  
Molecular Damage

Population aging results in urgent needs of interventions aimed at ensuring healthy senescence. Exercise often results in healthy aging, yet many molecular mechanisms underlying such effects still need to be identified. We here investigated whether the age-dependent accumulation of oxidative and methylglyoxal- (MG-) related molecular damage could be delayed by moderate exercise in the mouse ovary, an organ that first exhibits impaired function with advancing age in mammals. CD1 female mice underwent two- or four-month treadmill-based running through the transition from adult to middle age, when ovaries show signs of senescence, and markers of protection against reactive oxygen species (ROS) and MG were measured. The long-term exercise reduced the protein oxidative damage in the ovaries (P<0.01), and this was linked to the preservation of the glutathione peroxidase protection against ROS (P<0.001), as well as to the increased glutathione availability (P<0.001). Conversely, even though the age-related deactivation of the MG-targeting systems was partially prevented by the long-term running programme (P<0.001), exercised mice were not protected from the age-dependent glycative burden. In summary, lately initiated regular and moderate exercise limited some changes occurring in the ovaries of middle-aged mice, and this might help to develop nonpharmacological cointerventions to reduce the vulnerability of mammalian ovaries towards redox dysfunctions.

scholarly journals Environmental Contaminants Acting as Endocrine Disruptors Modulate Atherogenic Processes: New Risk Factors for Cardiovascular Diseases in Women?

Biomolecules ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 44
Author(s):  
Silvia Migliaccio ◽  
Viviana M. Bimonte ◽  
Zein Mersini Besharat ◽  
Claudia Sabato ◽  
Andrea Lenzi ◽  
...  
Keyword(s):  
Cardiovascular Diseases ◽  
Endocrine Disruptors ◽  
Successful Aging ◽  
Molecular Mechanisms ◽  
Potential Role ◽  
Unhealthy Lifestyle ◽  
Age Related ◽  
Increased Risk ◽  
Artery Disease

The number of aged individuals is increasing worldwide, rendering essential the comprehension of pathophysiological mechanisms of age-related alterations, which could facilitate the development of interventions contributing to “successful aging” and improving quality of life. Cardiovascular diseases (CVD) include pathologies affecting the heart or blood vessels, such as hypertension, peripheral artery disease and coronary heart disease. Indeed, age-associated modifications in body composition, hormonal, nutritional and metabolic factors, as well as a decline in physical activity are all involved in the increased risk of developing atherogenic alterations that raise the risk of CVD development. Several factors have been reported to play a role in the alterations observed in muscle and endothelial cells and that lead to increased CVD, such as genetic pattern, smoking and unhealthy lifestyle. Moreover, a difference in the risk of these diseases in women and men has been reported. Interestingly, in the past decades attention has been focused on a potential role of several pollutants that disrupt human health by interfering with hormonal pathways, and more specifically in non-communicable diseases such as obesity, diabetes and CVD. This review will focus on the potential alteration induced by Endocrine Disruptors (Eds) in the attempt to characterize a potential role in the cellular and molecular mechanisms involved in the atheromatous degeneration process and CVD progression.

scholarly journals Assessment of the Potential Role of Tryptophan as the Precursor of Serotonin and Melatonin for the Aged Sleep-wake Cycle and Immune Function: Streptopelia Risoria as a Model

2009 ◽  
Vol 2 ◽  
pp. IJTR.S1129 ◽  
Author(s):  
Sergio D. Paredes ◽  
Carmen Barriga ◽  
Russel J. Reiter ◽  
Ana B. Rodríguez
Keyword(s):  
Immune Response ◽  
Potential Role ◽  
Suitable Model ◽  
Streptopelia Risoria ◽  
Age Related ◽  
Amino Acid Tryptophan ◽  
The Relationship ◽  
The Brain ◽  
Circulating Levels

In the present review we summarize the relationship between the amino acid, tryptophan, the neurotransmitter, serotonin, and the indole, melatonin, with the rhythms of sleep/wake and the immune response along with the possible connections between the alterations in these rhythms due to aging and the so-called “serotonin and melatonin deficiency state.” The decrease associated with aging of the brain and circulating levels of serotonin and melatonin seemingly contributes to the alterations of both the sleep/wake cycle and the immune response that typically accompany old age. The supplemental administration of tryptophan, e.g. the inclusion of tryptophan-enriched food in the diet, might help to remediate these age-related alterations due to its capacity of raise the serotonin and melatonin levels in the brain and blood. Herein, we also summarize a set of studies related to the potential role that tryptophan, and its derived product melatonin, may play in the restoration of the aged circadian rhythms of sleep/wake and immune response, taking the ringdove ( Streptopelia risoria) as a suitable model.

Long-term management of patients with multiple brain metastases after shaped beam radiosurgery

2004 ◽  
pp. 406-412
Author(s):  
Paul Okunieff ◽  
Michael C. Schell ◽  
Russell Ruo ◽  
E. Ronald Hale ◽  
Walter G. O'Dell ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Tumor Control ◽  
Content Type ◽  
Negative Results ◽  
Multiple Metastases ◽  
Extracranial Disease ◽  
Successful Control ◽  
The Brain

✓ The role of radiosurgery in the treatment of patients with advanced-stage metastatic disease is currently under debate. Previous randomized studies have not consistently supported the use of radiosurgery to treat patients with numbers of brain metastases. In negative-results studies, however, intracranial tumor control was high but extracranial disease progressed; thus, patient survival was not greatly affected, although neurocognitive function was generally maintained until death. Because the future promises improved systemic (extracranial) therapy, the successful control of brain disease is that much more crucial. Thus, for selected patients with multiple metastases to the brain who remain in good neurological condition, aggressive lesion-targeting radiosurgery should be very useful. Although a major limitation to success of this therapy is the lack of control of extracranial disease in most patients, it is clear that well-designed, aggressive treatment substantially decreases the progression of brain metastases and also improves neurocognitive survival. The authors present the management and a methodology for rational treatment of a patient with breast cancer who has harbored 24 brain metastases during a 3-year period.

Neurotoxic and Neuroprotective Role of Exosomes in Parkinson’s Disease

2020 ◽  
Vol 25 (42) ◽  
pp. 4510-4522 ◽  
Author(s):  
Biancamaria Longoni ◽  
Irene Fasciani ◽  
Shivakumar Kolachalam ◽  
Ilaria Pietrantoni ◽  
Francesco Marampon ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Potential Role ◽  
Current Knowledge ◽  
Biological Fluids ◽  
Cell Communication ◽  
Target Cells ◽  
Cellular Debris ◽  
The Brain

: Exosomes are extracellular vesicles produced by eukaryotic cells that are also found in most biological fluids and tissues. While they were initially thought to act as compartments for removal of cellular debris, they are now recognized as important tools for cell-to-cell communication and for the transfer of pathogens between the cells. They have attracted particular interest in neurodegenerative diseases for their potential role in transferring prion-like proteins between neurons, and in Parkinson’s disease (PD), they have been shown to spread oligomers of α-synuclein in the brain accelerating the progression of this pathology. A potential neuroprotective role of exosomes has also been equally proposed in PD as they could limit the toxicity of α-synuclein by clearing them out of the cells. Exosomes have also attracted considerable attention for use as drug vehicles. Being nonimmunogenic in nature, they provide an unprecedented opportunity to enhance the delivery of incorporated drugs to target cells. In this review, we discuss current knowledge about the potential neurotoxic and neuroprotective role of exosomes and their potential application as drug delivery systems in PD.

Sign in / Sign up

Export Citation Format

Share Document