scholarly journals Molecular and cellular pathways contributing to brain aging

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Aliabbas Zia ◽  
Ali Mohammad Pourbagher-Shahri ◽  
Tahereh Farkhondeh ◽  
Saeed Samarghandian
Keyword(s):  
Neurodegenerative Diseases ◽  
Neurodegenerative Disorders ◽  
Brain Aging ◽  
Neuroprotective Effect ◽  
Ros Generation ◽  
Brain Health ◽  
Cellular Pathways ◽  
Aging Mechanisms ◽  
Oxidatively Modified ◽  
Biology Of Aging

AbstractAging is the leading risk factor for several age-associated diseases such as neurodegenerative diseases. Understanding the biology of aging mechanisms is essential to the pursuit of brain health. In this regard, brain aging is defined by a gradual decrease in neurophysiological functions, impaired adaptive neuroplasticity, dysregulation of neuronal Ca2+ homeostasis, neuroinflammation, and oxidatively modified molecules and organelles. Numerous pathways lead to brain aging, including increased oxidative stress, inflammation, disturbances in energy metabolism such as deregulated autophagy, mitochondrial dysfunction, and IGF-1, mTOR, ROS, AMPK, SIRTs, and p53 as central modulators of the metabolic control, connecting aging to the pathways, which lead to neurodegenerative disorders. Also, calorie restriction (CR), physical exercise, and mental activities can extend lifespan and increase nervous system resistance to age-associated neurodegenerative diseases. The neuroprotective effect of CR involves increased protection against ROS generation, maintenance of cellular Ca2+ homeostasis, and inhibition of apoptosis. The recent evidence about the modem molecular and cellular methods in neurobiology to brain aging is exhibiting a significant potential in brain cells for adaptation to aging and resistance to neurodegenerative disorders.

scholarly journals Physical Activity and Brain Health

Genes ◽  
2019 ◽  
Vol 10 (9) ◽  
pp. 720 ◽  
Author(s):  
Di Liegro ◽  
Schiera ◽  
Proia ◽  
Di Liegro
Keyword(s):  
Gene Expression ◽  
Physical Activity ◽  
Cognitive Processes ◽  
Sedentary Lifestyle ◽  
Brain Aging ◽  
Brain Health ◽  
Metabolic Outcomes ◽  
Antidepressant Effects ◽  
Cellular Pathways ◽  
Sound Mind

Physical activity (PA) has been central in the life of our species for most of its history, and thus shaped our physiology during evolution. However, only recently the health consequences of a sedentary lifestyle, and of highly energetic diets, are becoming clear. It has been also acknowledged that lifestyle and diet can induce epigenetic modifications which modify chromatin structure and gene expression, thus causing even heritable metabolic outcomes. Many studies have shown that PA can reverse at least some of the unwanted effects of sedentary lifestyle, and can also contribute in delaying brain aging and degenerative pathologies such as Alzheimer’s Disease, diabetes, and multiple sclerosis. Most importantly, PA improves cognitive processes and memory, has analgesic and antidepressant effects, and even induces a sense of wellbeing, giving strength to the ancient principle of “mens sana in corpore sano” (i.e., a sound mind in a sound body). In this review we will discuss the potential mechanisms underlying the effects of PA on brain health, focusing on hormones, neurotrophins, and neurotransmitters, the release of which is modulated by PA, as well as on the intra- and extra-cellular pathways that regulate the expression of some of the genes involved.

scholarly journals Therapeutic Potential of AAV1-Rheb(S16H) Transduction against Neurodegenerative Diseases

2021 ◽  
Vol 22 (6) ◽  
pp. 3064
Author(s):  
Youngpyo Nam ◽  
Gyeong Joon Moon ◽  
Sang Ryong Kim
Keyword(s):  
Neurodegenerative Diseases ◽  
Neurodegenerative Disorders ◽  
Therapeutic Potential ◽  
Neuroprotective Effect ◽  
Active Form ◽  
Mammalian Target Of Rapamycin ◽  
Regulatory System ◽  
Neuronal Population ◽  
Vital Role

Neurotrophic factors (NTFs) are essential for cell growth, survival, synaptic plasticity, and maintenance of specific neuronal population in the central nervous system. Multiple studies have demonstrated that alterations in the levels and activities of NTFs are related to the pathology and symptoms of neurodegenerative disorders, such as Parkinson’s disease (PD), Alzheimer’s disease (AD), and Huntington’s disease. Hence, the key molecule that can regulate the expression of NTFs is an important target for gene therapy coupling adeno-associated virus vector (AAV) gene. We have previously reported that the Ras homolog protein enriched in brain (Rheb)–mammalian target of rapamycin complex 1 (mTORC1) axis plays a vital role in preventing neuronal death in the brain of AD and PD patients. AAV transduction using a constitutively active form of Rheb exerts a neuroprotective effect through the upregulation of NTFs, thereby promoting the neurotrophic interaction between astrocytes and neurons in AD conditions. These findings suggest the role of Rheb as an important regulator of the regulatory system of NTFs to treat neurodegenerative diseases. In this review, we present an overview of the role of Rheb in neurodegenerative diseases and summarize the therapeutic potential of AAV serotype 1 (AAV1)-Rheb(S16H) transduction in the treatment of neurodegenerative disorders, focusing on diseases, such as AD and PD.

scholarly journals The Role of NADPH Oxidases and Oxidative Stress in Neurodegenerative Disorders

2018 ◽  
Vol 19 (12) ◽  
pp. 3824 ◽  
Author(s):  
Anuradha Tarafdar ◽  
Giordano Pula
Keyword(s):  
Oxidative Stress ◽  
Neurodegenerative Diseases ◽  
Neurodegenerative Disorders ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Ros Generation ◽  
Phagocytic Cells ◽  
Nadph Oxidases ◽  
Age Related ◽  
Recent Developments ◽  
Cerebrovascular Endothelial Cells

For a number of years, nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOX) was synonymous with NOX2/gp91phox and was considered to be a peculiarity of professional phagocytic cells. Over the last decade, several more homologs have been identified and based on current research, the NOX family consists of NOX1, NOX2, NOX3, NOX4, NOX5, DUOX1 and DUOX2 enzymes. NOXs are electron transporting membrane proteins that are responsible for reactive oxygen species (ROS) generation—primarily superoxide anion (O2●−), although hydrogen peroxide (H2O2) can also be generated. Elevated ROS leads to oxidative stress (OS), which has been associated with a myriad of inflammatory and degenerative pathologies. Interestingly, OS is also the commonality in the pathophysiology of neurodegenerative disorders, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS). NOX enzymes are expressed in neurons, glial cells and cerebrovascular endothelial cells. NOX-mediated OS is identified as one of the main causes of cerebrovascular damage in neurodegenerative diseases. In this review, we will discuss recent developments in our understanding of the mechanisms linking NOX activity, OS and neurodegenerative diseases, with particular focus on the neurovascular component of these conditions. We conclude highlighting current challenges and future opportunities to combat age-related neurodegenerative disorders by targeting NOXs.

scholarly journals Neuroprotective Potential of GDF11: Myth or Reality?

2019 ◽  
Vol 20 (14) ◽  
pp. 3563 ◽  
Author(s):  
Luc Rochette ◽  
Gabriel Malka
Keyword(s):  
Neurodegenerative Diseases ◽  
Blood Plasma ◽  
Neurodegenerative Disorders ◽  
Brain Aging ◽  
Therapeutic Strategies ◽  
Blood Concentrations ◽  
Age Related ◽  
Novel Therapeutic Strategies ◽  
The Brain ◽  
Novel Therapeutic

In the brain, aging is accompanied by cellular and functional deficiencies that promote vulnerability to neurodegenerative disorders. In blood plasma from young and old animals, various factors such as growth differentiation factor 11 (GDF11), whose levels are elevated in young animals, have been identified. The blood concentrations of these factors appear to be inversely correlated with the age-related decline of neurogenesis. The identification of GDF11 as a “rejuvenating factor” opens up perspectives for the treatment of neurodegenerative diseases. As a pro-neurogenic and pro-angiogenic agent, GDF11 may constitute a basis for novel therapeutic strategies.

scholarly journals Towards an understanding of women's brain aging: the immunology of pregnancy and menopause

2020 ◽  
Author(s):  
Claudia Barth ◽  
Ann-Marie G de Lange
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Sex Differences ◽  
Neurodegenerative Diseases ◽  
Brain Aging ◽  
Brain Health ◽  
Critical Part ◽  
Autoimmune Conditions ◽  
Specific Factors ◽  
Female Specific

Women are at significantly greater risk of developing Alzheimer's disease and show higher prevalence of autoimmune conditions relative to men. Women's brain health is historically understudied, and little is therefore known about the mechanisms underlying epidemiological sex differences in neurodegenerative diseases, and how female-specific factors may influence women's brain health across the lifespan. In this review, we summarize recent studies on the immunology of pregnancy and menopause, emphasizing that these major immunological and hormonal transition phases may play a critical part in women's brain aging trajectories.

scholarly journals THE BIOLOGICAL ROLE OF MITOCHONDRIA IN BODY AGING

2015 ◽  
pp. 8-13
Author(s):  
N. E. Fomchenko ◽  
E. V. Voropayev ◽  
A. V. Skachkov ◽  
N. Yu. Zatora
Keyword(s):  
Neurodegenerative Disorders ◽  
Evolutionary Genetics ◽  
Scientific Discipline ◽  
Mitochondrial Medicine ◽  
Leading Role ◽  
Genetic Features ◽  
Genetic Mechanisms ◽  
Aging Mechanisms ◽  
Biology Of Aging

Life expectancy is a complex factor, and identification of genetic mechanisms of its formation is one of the fundamental problems in developmental biology, evolutionary genetics, and molecular gerontology. The task of the biology of aging includes elucidation of the aging mechanisms, which are diverse and involve mechanical deterioration of organism, elucidation of the genetic features of the structure and functioning of the DNA nucleus and cytoplasmic organelles - mitochondria. Currently mitochondrial genetics is an independent scientific discipline. The discovery of the leading role of mitochondria in sensitivity to drugs, their key role in aging and neurodegenerative disorders of apoptosis led to the creation of mitochondrial medicine, which studies diseases associated with mitochondrial dysfunction.

scholarly journals SIRT6 Through the Brain Evolution, Development, and Aging

2021 ◽  
Vol 13 ◽  
Author(s):  
Alfredo Garcia-Venzor ◽  
Debra Toiber
Keyword(s):  
Embryonic Development ◽  
Neurodegenerative Diseases ◽  
Brain Development ◽  
Aging Process ◽  
Brain Aging ◽  
Brain Evolution ◽  
Loss Of Function ◽  
Brain Health ◽  
Development And Aging ◽  
The Brain

During an organism’s lifespan, two main phenomena are critical for the organism’s survival. These are (1) a proper embryonic development, which permits the new organism to function with high fitness, grow and reproduce, and (2) the aging process, which will progressively undermine its competence and fitness for survival, leading to its death. Interestingly these processes present various similarities at the molecular level. Notably, as organisms became more complex, regulation of these processes became coordinated by the brain, and failure in brain activity is detrimental in both development and aging. One of the critical processes regulating brain health is the capacity to keep its genomic integrity and epigenetic regulation—deficiency in DNA repair results in neurodevelopmental and neurodegenerative diseases. As the brain becomes more complex, this effect becomes more evident. In this perspective, we will analyze how the brain evolved and became critical for human survival and the role Sirt6 plays in brain health. Sirt6 belongs to the Sirtuin family of histone deacetylases that control several cellular processes; among them, Sirt6 has been associated with the proper embryonic development and is associated with the aging process. In humans, Sirt6 has a pivotal role during brain aging, and its loss of function is correlated with the appearance of neurodegenerative diseases such as Alzheimer’s disease. However, Sirt6 roles during brain development and aging, especially the last one, are not observed in all species. It appears that during the brain organ evolution, Sirt6 has gained more relevance as the brain becomes bigger and more complex, observing the most detrimental effect in the brains of Homo sapiens. In this perspective, we part from the evolution of the brain in metazoans, the biological similarities between brain development and aging, and the relevant functions of Sirt6 in these similar phenomena to conclude with the evidence suggesting a more relevant role of Sirt6 gained in the brain evolution.

scholarly journals Beneficial Effects on Brain Micro-Environment by Caloric Restriction in Alleviating Neurodegenerative Diseases and Brain Aging

2021 ◽  
Vol 12 ◽  
Author(s):  
Li Zhang ◽  
Huachong Xu ◽  
Ning Ding ◽  
Xue Li ◽  
Xiaoyin Chen ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Caloric Restriction ◽  
Metabolic Disorders ◽  
Brain Aging ◽  
Future Perspectives ◽  
Brain Health ◽  
Neuroprotective Effects ◽  
Beneficial Effects ◽  
Extracellular Microenvironment

Aging and neurodegenerative diseases are frequently associated with the disruption of the extracellular microenvironment, which includes mesenchyme and body fluid components. Caloric restriction (CR) has been recognized as a lifestyle intervention that can improve long-term health. In addition to preventing metabolic disorders, CR has been shown to improve brain health owing to its enhancing effect on cognitive functions or retarding effect on the progression of neurodegenerative diseases. This article summarizes current findings regarding the neuroprotective effects of CR, which include the modulation of metabolism, autophagy, oxidative stress, and neuroinflammation. This review may offer future perspectives for brain aging interventions.

Natural Products for the Treatment of Neurodegenerative Diseases

2020 ◽  
Vol 27 (34) ◽  
pp. 5790-5828 ◽  
Author(s):  
Ze Wang ◽  
Chunyang He ◽  
Jing-Shan Shi
Keyword(s):  
Nervous System ◽  
Natural Products ◽  
Neurodegenerative Diseases ◽  
Neuroprotective Effect ◽  
Rapid Development ◽  
New Drugs ◽  
Progressive Degeneration ◽  
Cord Injury ◽  
The Central Nervous System ◽  
And Function

Neurodegenerative diseases are a heterogeneous group of disorders characterized by the progressive degeneration of the structure and function of the central nervous system or peripheral nervous system. Alzheimer's Disease (AD), Parkinson's Disease (PD) and Spinal Cord Injury (SCI) are the common neurodegenerative diseases, which typically occur in people over the age of 60. With the rapid development of an aged society, over 60 million people worldwide are suffering from these uncurable diseases. Therefore, the search for new drugs and therapeutic methods has become an increasingly important research topic. Natural products especially those from the Traditional Chinese Medicines (TCMs), are the most important sources of drugs, and have received extensive interest among pharmacist. In this review, in order to facilitate further chemical modification of those useful natural products by pharmacists, we will bring together recent studies in single natural compound from TCMs with neuroprotective effect.

Purines and Pyrimidines: Metabolism, Function and Potential as therapeutic options in neurodegenerative diseases

2020 ◽  
Vol 21 ◽  
Author(s):  
Debanjan Kundu ◽  
Vikash Kumar Dubey
Keyword(s):  
Neurodegenerative Diseases ◽  
Neurodegenerative Disorders ◽  
Protein Misfolding ◽  
Molecular Mechanisms ◽  
Treatment Regimens ◽  
Loss Of Balance ◽  
Current Scenario ◽  
Unexplored Area ◽  
Molecular Origin ◽  
Purines And Pyrimidines

Abstract:: Various neurodegenerative disorders have molecular origin but some common molecular mechanisms. In the current scenario, there are very few treatment regimens present for advanced neurodegenerative diseases. In this context, there is an urgent need for alternate options in the form of natural compounds with an ameliorating effect on patients. There have been individual scattered experiments trying to identify potential values of various intracellular metabolites. Purines and Pyrimidines, which are vital molecules governing various aspects of cellular biochemical reactions, have been long sought as crucial candidates for the same, but there are still many questions that go unanswered. Some critical functions of these molecules associated with neuromodulation activities have been identified. They are also known to play a role in foetal neurodevelopment, but there is a lacuna in understanding their mechanisms. In this review, we have tried to assemble and identify the importance of purines and pyrimidines, connecting them with the prevalence of neurodegenerative diseases. The leading cause of this class of diseases is protein misfolding and the formation of amyloids. A direct correlation between loss of balance in cellular homeostasis and amyloidosis is yet an unexplored area. This review aims at bringing the current literature available under one umbrella serving as a foundation for further extensive research in this field of drug development in neurodegenerative diseases.

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