Advances in PPARs Molecular Dynamics and Glitazones as a Repurposing Therapeutic Strategy through Mitochondrial Redox Dynamics against Neurodegeneration

2021 ◽  
Vol 19 ◽  
Author(s):  
Priya Durai ◽  
Narasimha M. Beeraka ◽  
Hemanth Vikram ◽  
Prakash Krishnan ◽  
Pranesh Gudur ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Mitochondrial Dynamics ◽  
Redox System ◽  
Ppar Gamma ◽  
Therapeutic Effects ◽  
Peroxisome Proliferator ◽  
Human Beings ◽  
Brain Physiology ◽  
The Brain

: Peroxisome proliferator activated receptors (PPARs) activity exhibit significant implications for the development of novel therapeutic modalities against neurodegenerative diseases. PPAR-α, PPAR-β/δ, and PPAR-γ nuclear receptors expression are significantly reported in the brain, their implications in brain physiology and other neurodegenerative diseases still require extensive studies. PPAR signaling can modulate various cell signaling mechanisms involved inside the cells contributing to on- and -off target actions selectively to promote therapeutic effects as well as the adverse effects of PPAR ligands. Both natural and synthetic ligands for the PPARα, PPARγ, and PPARβ/δ have been reported. PPARα (WY 14.643) and PPARγ agonists can confer neuroprotection by modulating mitochondrial dynamics through the redox system. The pharmacological effect of these agonists may deliver effective clinical responses by protecting vulnerable neurons to Aβ toxicity in Alzheimer’s disease (AD) patients. Therefore, the current review delineated the ligands interaction with 3D- PPARs to modulate neuroprotection and also deciphered the efficacy of numerous drugs viz., Aβ aggregation inhibitors, vaccines, and γ-secretase inhibitors against AD; this review elucidated the role of PPAR and their receptor isoforms in neural systems, and neurodegeneration in human beings. Further, we have substantially discussed the efficacy of PPREs as potent transcription factors in the brain, and the role of PPAR agonists in neurotransmission, PPAR gamma coactivator-1α (PGC-1α), and mitochondrial dynamics in neuroprotection during AD conditions. This review concludes with the statement; development of novel PPARs agonists may benefit patients with neurodegeneration mainly in AD patients to mitigate the pathophysiology & dementia subsequently to improve overall patient’s quality of life.

scholarly journals PPAR Gamma and Viral Infections of the Brain

2021 ◽  
Vol 22 (16) ◽  
pp. 8876
Author(s):  
Pierre Layrolle ◽  
Pierre Payoux ◽  
Stéphane Chavanas
Keyword(s):  
Viral Infections ◽  
Ppar Gamma ◽  
Brain Parenchyma ◽  
Peroxisome Proliferator ◽  
Neural Cells ◽  
Peroxisome Proliferator Activated Receptor ◽  
Immunodeficiency Virus ◽  
Health And Disease ◽  
The Brain

Peroxisome Proliferator-Activated Receptor gamma (PPARγ) is a master regulator of metabolism, adipogenesis, inflammation and cell cycle, and it has been extensively studied in the brain in relation to inflammation or neurodegeneration. Little is known however about its role in viral infections of the brain parenchyma, although they represent the most frequent cause of encephalitis and are a major threat for the developing brain. Specific to viral infections is the ability to subvert signaling pathways of the host cell to ensure virus replication and spreading, as deleterious as the consequences may be for the host. In this respect, the pleiotropic role of PPARγ makes it a critical target of infection. This review aims to provide an update on the role of PPARγ in viral infections of the brain. Recent studies have highlighted the involvement of PPARγ in brain or neural cells infected by immunodeficiency virus 1, Zika virus, or human cytomegalovirus. They have provided a better understanding on PPARγ functions in the infected brain, and revealed that it can be a double-edged sword with respect to inflammation, viral replication, or neuronogenesis. They unraveled new roles of PPARγ in health and disease and could possibly help designing new therapeutic strategies.

scholarly journals Mesenchymal Stem Cell Derived Extracellular Vesicles for Repairing the Neurovascular Unit after Ischemic Stroke

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 767
Author(s):  
Courtney Davis ◽  
Sean I. Savitz ◽  
Nikunj Satani
Keyword(s):  
Ischemic Stroke ◽  
Extracellular Vesicles ◽  
Neurovascular Unit ◽  
Culture Conditions ◽  
Therapeutic Effects ◽  
Stroke Treatment ◽  
Inflammatory Molecules ◽  
The Brain

Ischemic stroke is a debilitating disease and one of the leading causes of long-term disability. During the early phase after ischemic stroke, the blood-brain barrier (BBB) exhibits increased permeability and disruption, leading to an influx of immune cells and inflammatory molecules that exacerbate the damage to the brain tissue. Mesenchymal stem cells have been investigated as a promising therapy to improve the recovery after ischemic stroke. The therapeutic effects imparted by MSCs are mostly paracrine. Recently, the role of extracellular vesicles released by these MSCs have been studied as possible carriers of information to the brain. This review focuses on the potential of MSC derived EVs to repair the components of the neurovascular unit (NVU) controlling the BBB, in order to promote overall recovery from stroke. Here, we review the techniques for increasing the effectiveness of MSC-based therapeutics, such as improved homing capabilities, bioengineering protein expression, modified culture conditions, and customizing the contents of EVs. Combining multiple techniques targeting NVU repair may provide the basis for improved future stroke treatment paradigms.

scholarly journals From Exercise to Cognitive Performance: Role of Irisin

2021 ◽  
Vol 11 (15) ◽  
pp. 7120
Author(s):  
Mirko Pesce ◽  
Irene La Fratta ◽  
Teresa Paolucci ◽  
Alfredo Grilli ◽  
Antonia Patruno ◽  
...  
Keyword(s):  
The Elderly ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Beneficial Effects ◽  
General Exercise ◽  
Fibronectin Type Iii ◽  
Exercise Induced ◽  
Fibronectin Type Iii Domain ◽  
The Brain

The beneficial effects of exercise on the brain are well known. In general, exercise offers an effective way to improve cognitive function in all ages, particularly in the elderly, who are considered the most vulnerable to neurodegenerative disorders. In this regard, myokines, hormones secreted by muscle in response to exercise, have recently gained attention as beneficial mediators. Irisin is a novel exercise-induced myokine, that modulates several bodily processes, such as glucose homeostasis, and reduces systemic inflammation. Irisin is cleaved from fibronectin type III domain containing 5 (FNDC5), a transmembrane precursor protein expressed in muscle under the control of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α). The FNDC5/irisin system is also expressed in the hippocampus, where it stimulates the expression of the neurotrophin brain-derived neurotrophic factor in this area that is associated with learning and memory. In this review, we aimed to discuss the role of irisin as a key mediator of the beneficial effects of exercise on synaptic plasticity and memory in the elderly, suggesting its roles within the main promoters of the beneficial effects of exercise on the brain.

scholarly journals News about the Role of Fluid and Imaging Biomarkers in Neurodegenerative Diseases

Biomedicines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 252
Author(s):  
Jacopo Meldolesi
Keyword(s):  
Neurodegenerative Diseases ◽  
Imaging Techniques ◽  
Imaging Biomarkers ◽  
Positron Emission ◽  
Specific Proteins ◽  
Great Relevance ◽  
The Brain ◽  
Positive Point

Biomarkers are molecules that are variable in their origin, nature, and mechanism of action; they are of great relevance in biology and also in medicine because of their specific connection with a single or several diseases. Biomarkers are of two types, which in some cases are operative with each other. Fluid biomarkers, started around 2000, are generated in fluid from specific proteins/peptides and miRNAs accumulated within two extracellular fluids, either the central spinal fluid or blood plasma. The switch of these proteins/peptides and miRNAs, from free to segregated within extracellular vesicles, has induced certain advantages including higher levels within fluids and lower operative expenses. Imaging biomarkers, started around 2004, are identified in vivo upon their binding by radiolabeled molecules subsequently revealed in the brain by positron emission tomography and/or other imaging techniques. A positive point for the latter approach is the quantitation of results, but expenses are much higher. At present, both types of biomarker are being extensively employed to study Alzheimer’s and other neurodegenerative diseases, investigated from the presymptomatic to mature stages. In conclusion, biomarkers have revolutionized scientific and medical research and practice. Diagnosis, which is often inadequate when based on medical criteria only, has been recently improved by the multiplicity and specificity of biomarkers. Analogous results have been obtained for prognosis. In contrast, improvement of therapy has been limited or fully absent, especially for Alzheimer’s in which progress has been inadequate. An urgent need at hand is therefore the progress of a new drug trial design together with patient management in clinical practice.

scholarly journals The Role of Long Noncoding RNAs in Diabetic Alzheimer’s Disease

2018 ◽  
Vol 7 (11) ◽  
pp. 461 ◽  
Author(s):  
Young-Kook Kim ◽  
Juhyun Song
Keyword(s):  
Alzheimer’S Disease ◽  
Insulin Resistance ◽  
Alzheimer's Disease ◽  
Neurodegenerative Diseases ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Glucose Dysregulation ◽  
Near Future ◽  
The Brain

Long noncoding RNAs (lncRNAs) are involved in diverse physiological and pathological processes by modulating gene expression. They have been found to be dysregulated in the brain and cerebrospinal fluid of patients with neurodegenerative diseases, and are considered promising therapeutic targets for treatment. Among the various neurodegenerative diseases, diabetic Alzheimer’s disease (AD) has been recently emerging as an important issue due to several unexpected reports suggesting that metabolic issues in the brain, such as insulin resistance and glucose dysregulation, could be important risk factors for AD. To facilitate understanding of the role of lncRNAs in this field, here we review recent studies on lncRNAs in AD and diabetes, and summarize them with different categories associated with the pathogenesis of the diseases including neurogenesis, synaptic dysfunction, amyloid beta accumulation, neuroinflammation, insulin resistance, and glucose dysregulation. It is essential to understand the role of lncRNAs in the pathogenesis of diabetic AD from various perspectives for therapeutic utilization of lncRNAs in the near future.

ATP-binding cassette transporters and neurodegenerative diseases

2021 ◽  
Author(s):  
Jared S. Katzeff ◽  
Woojin Scott Kim
Keyword(s):  
Neurodegenerative Diseases ◽  
Abc Transporters ◽  
Brain Diseases ◽  
Atp Binding ◽  
Future Directions ◽  
Diverse Range ◽  
The Brain ◽  
Lateral Sclerosis ◽  
Atp Binding Cassette

Abstract ATP-binding cassette (ABC) transporters are one of the largest groups of transporter families in humans. ABC transporters mediate the translocation of a diverse range of substrates across cellular membranes, including amino acids, nucleosides, lipids, sugars and xenobiotics. Neurodegenerative diseases are a group of brain diseases that detrimentally affect neurons and other brain cells and are usually associated with deposits of pathogenic proteins in the brain. Major neurodegenerative diseases include Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis. ABC transporters are highly expressed in the brain and have been implicated in a number of pathological processes underlying neurodegenerative diseases. This review outlines the current understanding of the role of ABC transporters in neurodegenerative diseases, focusing on some of the most important pathways, and also suggests future directions for research in this field.

Could Emotions Be Modelled through Information Processing?

2015 ◽  
pp. 63-82
Author(s):  
Ebrahim Oshni Alvandi
Keyword(s):  
Information Processing ◽  
Cognitive Processes ◽  
Environmental Variables ◽  
Emotional Processing ◽  
Processing System ◽  
Human Beings ◽  
Context Sensitive ◽  
Emotional Agents ◽  
The Brain

One way to evaluate cognitive processes in living or nonliving systems is by using the notion of “information processing”. Emotions as cognitive processes orient human beings to recognize, express and display themselves or their wellbeing through dynamical and adaptive form of information processing. In addition, humans behave or act emotionally in an embodied environment. The brain embeds symbols, meaning and purposes for emotions as well. So any model of natural or autonomous emotional agents/systems needs to consider the embodied features of emotions that are processed in an informational channel of the brain or a processing system. This analytical and explanatory study described in this chapter uses the pragmatic notion of information to develop a theoretical model for emotions that attempts to synthesize some essential aspects of human emotional processing. The model holds context-sensitive and purpose-based features of emotional pattering in the brain. The role of memory is discussed and an idea of control parameters that have roles in processing environmental variables in emotional patterning is introduced.

scholarly journals Activate or Inhibit? Implications of Autophagy Modulation as a Therapeutic Strategy for Alzheimer’s Disease

2020 ◽  
Vol 21 (18) ◽  
pp. 6739
Author(s):  
Sharmeelavathi Krishnan ◽  
Yasaswi Shrestha ◽  
Dona P. W. Jayatunga ◽  
Sarah Rea ◽  
Ralph Martins ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Diseases ◽  
Therapeutic Strategy ◽  
Senile Plaques ◽  
Physiological State ◽  
Proteotoxic Stress ◽  
Underlying Causes ◽  
The Brain

Neurodegenerative diseases result in a range of conditions depending on the type of proteinopathy, genes affected or the location of the degeneration in the brain. Proteinopathies such as senile plaques and neurofibrillary tangles in the brain are prominent features of Alzheimer’s disease (AD). Autophagy is a highly regulated mechanism of eliminating dysfunctional organelles and proteins, and plays an important role in removing these pathogenic intracellular protein aggregates, not only in AD, but also in other neurodegenerative diseases. Activating autophagy is gaining interest as a potential therapeutic strategy for chronic diseases featuring protein aggregation and misfolding, including AD. Although autophagy activation is a promising intervention, over-activation of autophagy in neurodegenerative diseases that display impaired lysosomal clearance may accelerate pathology, suggesting that the success of any autophagy-based intervention is dependent on lysosomal clearance being functional. Additionally, the effects of autophagy activation may vary significantly depending on the physiological state of the cell, especially during proteotoxic stress and ageing. Growing evidence seems to favour a strategy of enhancing the efficacy of autophagy by preventing or reversing the impairments of the specific processes that are disrupted. Therefore, it is essential to understand the underlying causes of the autophagy defect in different neurodegenerative diseases to explore possible therapeutic approaches. This review will focus on the role of autophagy during stress and ageing, consequences that are linked to its activation and caveats in modulating this pathway as a treatment.

scholarly journals Effects of Ketone Bodies on Brain Metabolism and Function in Neurodegenerative Diseases

2020 ◽  
Vol 21 (22) ◽  
pp. 8767
Author(s):  
Nicole Jacqueline Jensen ◽  
Helena Zander Wodschow ◽  
Malin Nilsson ◽  
Jørgen Rungby
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Diseases ◽  
Brain Metabolism ◽  
Ketone Bodies ◽  
Current Knowledge ◽  
Ketogenic Diets ◽  
Cognitive Benefits ◽  
The Brain

Under normal physiological conditions the brain primarily utilizes glucose for ATP generation. However, in situations where glucose is sparse, e.g., during prolonged fasting, ketone bodies become an important energy source for the brain. The brain’s utilization of ketones seems to depend mainly on the concentration in the blood, thus many dietary approaches such as ketogenic diets, ingestion of ketogenic medium-chain fatty acids or exogenous ketones, facilitate significant changes in the brain’s metabolism. Therefore, these approaches may ameliorate the energy crisis in neurodegenerative diseases, which are characterized by a deterioration of the brain’s glucose metabolism, providing a therapeutic advantage in these diseases. Most clinical studies examining the neuroprotective role of ketone bodies have been conducted in patients with Alzheimer’s disease, where brain imaging studies support the notion of enhancing brain energy metabolism with ketones. Likewise, a few studies show modest functional improvements in patients with Parkinson’s disease and cognitive benefits in patients with—or at risk of—Alzheimer’s disease after ketogenic interventions. Here, we summarize current knowledge on how ketogenic interventions support brain metabolism and discuss the therapeutic role of ketones in neurodegenerative disease, emphasizing clinical data.

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