scholarly journals Neurodegenerative Diseases: Multifactorial Conformational Diseases and Their Therapeutic Interventions

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Saba Sheikh ◽  
Safia ◽  
Ejazul Haque ◽  
Snober S. Mir
Keyword(s):  
Neurodegenerative Diseases ◽  
Neurodegenerative Disorders ◽  
Drug Targets ◽  
Molecular Mechanisms ◽  
Therapeutic Interventions ◽  
Conformational Diseases ◽  
Considerable Evidence ◽  
Recent Trends ◽  
Lateral Sclerosis

Neurodegenerative diseases are multifactorial debilitating disorders of the nervous system that affect approximately 30 millionindividuals worldwide. Neurodegenerative diseases such as Alzheimer’s, Parkinson’s, Huntington’s, and amyotrophic lateral sclerosis diseases are the consequence of misfolding and dysfunctional trafficking of proteins. Beside that, mitochondrial dysfunction, oxidative stress, and/or environmental factors strongly associated with age have also been implicated in causing neurodegeneration. After years of intensive research, considerable evidence has accumulated that demonstrates an important role of these factors in the etiology of common neurodegenerative diseases. Despite the extensive efforts that have attempted to define the molecular mechanisms underlying neurodegeneration, many aspects of these pathologies remain elusive. However, in order to explore the therapeutic interventions directed towards treatment of neurodegenerative diseases, neuroscientists are now fully exploiting the data obtained from studies of these basic mechanisms that have gone awry. The novelty of these mechanisms represents a challenge to the identification of viable drug targets and biomarkers for early diagnosis of the diseases. In this paper, we are reviewing various aspects associated with the disease and the recent trends that may have an application for the treatment of the neurodegenerative disorders.

scholarly journals Tau Accumulation via Reduced BAG3-mediated Autophagy Is Required for GGGGCC Repeat Expansion-Induced Neurodegeneration

2019 ◽  
Author(s):  
Xue Wen ◽  
Ping An ◽  
Hexuan Li ◽  
Zijian Zhou ◽  
Yimin Sun ◽  
...  
Keyword(s):  
Tau Protein ◽  
Neurodegenerative Disorders ◽  
Motor Performance ◽  
Molecular Mechanisms ◽  
Repeat Expansion ◽  
Cag Repeats ◽  
Reduced Activity ◽  
Lateral Sclerosis

SUMMARYExpansions of trinucleotide or hexanucleotide repeats lead to several neurodegenerative disorders including Huntington disease (HD, caused by the expanded CAG repeats (CAGr) in the HTT gene) and amyotrophic lateral sclerosis (ALS, could be caused by the expanded GGGGCC repeats (G4C2r) in the C9ORF72 gene), of which the molecular mechanisms remain unclear. Here we demonstrate that loss of the Drosophila orthologue of tau protein (dtau) significantly rescued in vivo neurodegeneration, motor performance impairments, and shortened life-span in Drosophila models expressing mutant HTT protein with expanded CAGr or the expanded G4C2r. Importantly, expression of human tau (htau4R) restored the disease-relevant phenotypes that were mitigated by the loss of dtau, suggesting a conserved role of tau in neurodegeneration. We further discovered that G4C2r expression increased dtau accumulation, possibly due to reduced activity of BAG3-mediated autophagy. Our study reveals a conserved role of tau in G4C2r-induced neurotoxicity in Drosophila models, providing mechanistic insights and potential therapeutic targets.

Role of medicinal plants against neurodegenerative diseases

2021 ◽  
Vol 22 ◽  
Author(s):  
Ritika Luthra ◽  
Arpita Roy
Keyword(s):  
Medicinal Plants ◽  
Neurodegenerative Diseases ◽  
Molecular Mechanisms ◽  
Environmental Changes ◽  
Inflammatory Responses ◽  
Vital Role ◽  
Significant Loss ◽  
Therapeutic Interventions ◽  
Inflammatory Stress

: Diseases with a significant loss of neurons, structurally and functionally are termed as neurodegenerative diseases. Due to the present therapeutic interventions and progressive nature of diseases, a variety of side effects have risen up, thus leading the patients to go for an alternative medication. The role of medicinal plants in such cases has been beneficial because of their exhibition via different cellular and molecular mechanisms. Alleviation in inflammatory responses, suppression of the functionary aspect of pro-inflammatory cytokines like a tumor, improvement in antioxidative properties is among few neuroprotective mechanisms of traditional plants. Variation in transcription and transduction pathways play a vital role in the preventive measures of plants in such diseases. Neurodegenerative diseases are generally caused by depletion of proteins, oxidative and inflammatory stress, environmental changes and so on, with aging being the most important cause. Natural compounds can be used in order to treat neurodegenerative diseases Medicinal plants such as Ginseng, Withania somnifera, Bacopa monnieri, Ginkgo biloba, etc. are some of the medicinal plants for prevention of neurological symptoms. This review deals with the use of different medicinal plants for the prevention of neurodegenerative diseases.

Mitochondria and Neurodegeneration

2007 ◽  
Vol 27 (1-3) ◽  
pp. 87-104 ◽  
Author(s):  
Lucia Petrozzi ◽  
Giulia Ricci ◽  
Noemi J. Giglioli ◽  
Gabriele Siciliano ◽  
Michelangelo Mancuso
Keyword(s):  
Alzheimer’S Disease ◽  
Amyotrophic Lateral Sclerosis ◽  
Neurodegenerative Diseases ◽  
Mitochondrial Dysfunction ◽  
Huntington's Disease ◽  
Neurodegenerative Disorders ◽  
Molecular Abnormalities ◽  
Lateral Sclerosis ◽  
Lines Of Evidence

Many lines of evidence suggest that mitochondria have a central role in ageing-related neurodegenerative diseases. However, despite the evidence of morphological, biochemical and molecular abnormalities in mitochondria in various tissues of patients with neurodegenerative disorders, the question “is mitochondrial dysfunction a necessary step in neurodegeneration?” is still unanswered. In this review, we highlight some of the major neurodegenerative disorders (Alzheimer's disease, Parkinson's disease, Amyotrophic lateral sclerosis and Huntington's disease) and discuss the role of the mitochondria in the pathogenetic cascade leading to neurodegeneration.

scholarly journals Mitophagy Regulates Neurodegenerative Diseases

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1876
Author(s):  
Xufeng Cen ◽  
Manke Zhang ◽  
Mengxin Zhou ◽  
Lingzhi Ye ◽  
Hongguang Xia
Keyword(s):  
Neurodegenerative Diseases ◽  
Signaling Pathways ◽  
Neurodegenerative Disorders ◽  
Essential Role ◽  
Molecular Mechanisms ◽  
Potential Role ◽  
Treatment Strategies ◽  
Metabolic Process ◽  
Recent Advances

Mitochondria play an essential role in supplying energy for the health and survival of neurons. Mitophagy is a metabolic process that removes dysfunctional or redundant mitochondria. This process preserves mitochondrial health. However, defective mitophagy triggers the accumulation of damaged mitochondria, causing major neurodegenerative disorders. This review introduces molecular mechanisms and signaling pathways behind mitophagy regulation. Furthermore, we focus on the recent advances in understanding the potential role of mitophagy in the pathogenesis of major neurodegenerative diseases (Parkinson’s, Alzheimer’s, Huntington’s, etc.) and aging. The findings will help identify the potential interventions of mitophagy regulation and treatment strategies of neurodegenerative diseases.

Molecular Mechanisms Underlying the Role of Mitophagy in Neurodegeneration

2020 ◽  
pp. 63-87
Author(s):  
Abhilasha Ahlawat ◽  
Meenakshi Kaira ◽  
Vaibhav Walia ◽  
Munish Garg
Keyword(s):  
Neurodegenerative Diseases ◽  
Signaling Pathways ◽  
Neurodegenerative Disorders ◽  
Molecular Mechanisms ◽  
Recent Literature ◽  
Therapeutic Activity ◽  
Efficient Removal ◽  
Selective Autophagy

Mitophagy is a selective autophagy process in which damaged or surplus mitochondria are removed to sustain normal homeostasis. The efficient removal of damaged or stressed mitochondria is crucial for cellular health. Recent literature emphasizes the role of PINK1-Parkin pathways in the pathogenesis process of various neurodegenerative disorders. Further, mitophagy has shown potential therapeutic activity in treating neurodegenerative diseases. Thus, mitophagy might be important in the field of pharmacotherapeutics. In the present chapter, the authors explain mitophagy, mitophagy signaling pathways, as well as mechanisms and roles of mitophagy in various neurodegenerative disorders.

scholarly journals Imaging Mass Spectrometry: A New Tool to Assess Molecular Underpinnings of Neurodegeneration

Metabolites ◽  
2019 ◽  
Vol 9 (7) ◽  
pp. 135 ◽  
Author(s):  
Kevin Chen ◽  
Dodge Baluya ◽  
Mehmet Tosun ◽  
Feng Li ◽  
Mirjana Maletic-Savatic
Keyword(s):  
Mass Spectrometry ◽  
Neurodegenerative Diseases ◽  
Molecular Mechanisms ◽  
New Technologies ◽  
A Priori ◽  
Imaging Mass Spectrometry ◽  
The Past ◽  
Wide Range ◽  
Lateral Sclerosis

Neurodegenerative diseases are prevalent and devastating. While extensive research has been done over the past decades, we are still far from comprehensively understanding what causes neurodegeneration and how we can prevent it or reverse it. Recently, systems biology approaches have led to a holistic examination of the interactions between genome, metabolome, and the environment, in order to shed new light on neurodegenerative pathogenesis. One of the new technologies that has emerged to facilitate such studies is imaging mass spectrometry (IMS). With its ability to map a wide range of small molecules with high spatial resolution, coupled with the ability to quantify them at once, without the need for a priori labeling, IMS has taken center stage in current research efforts in elucidating the role of the metabolome in driving neurodegeneration. IMS has already proven to be effective in investigating the lipidome and the proteome of various neurodegenerative diseases, such as Alzheimer’s, Parkinson’s, Huntington’s, multiple sclerosis, and amyotrophic lateral sclerosis. Here, we review the IMS platform for capturing biological snapshots of the metabolic state to shed more light on the molecular mechanisms of the diseased brain.

scholarly journals The Implication of Reticulons (RTNs) in Neurodegenerative Diseases: From Molecular Mechanisms to Potential Diagnostic and Therapeutic Approaches

2021 ◽  
Vol 22 (9) ◽  
pp. 4630
Author(s):  
Agnieszka Kulczyńska-Przybik ◽  
Piotr Mroczko ◽  
Maciej Dulewicz ◽  
Barbara Mroczko
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Neurodegenerative Diseases ◽  
Molecular Mechanisms ◽  
Therapeutic Approaches ◽  
Cord Injury ◽  
The Central Nervous System ◽  
Pleiotropic Functions ◽  
Lateral Sclerosis

Reticulons (RTNs) are crucial regulatory factors in the central nervous system (CNS) as well as immune system and play pleiotropic functions. In CNS, RTNs are transmembrane proteins mediating neuroanatomical plasticity and functional recovery after central nervous system injury or diseases. Moreover, RTNs, particularly RTN4 and RTN3, are involved in neurodegeneration and neuroinflammation processes. The crucial role of RTNs in the development of several neurodegenerative diseases, including Alzheimer’s disease (AD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), or other neurological conditions such as brain injury or spinal cord injury, has attracted scientific interest. Reticulons, particularly RTN-4A (Nogo-A), could provide both an understanding of early pathogenesis of neurodegenerative disorders and be potential therapeutic targets which may offer effective treatment or inhibit disease progression. This review focuses on the molecular mechanisms and functions of RTNs and their potential usefulness in clinical practice as a diagnostic tool or therapeutic strategy.

scholarly journals Microglial Potassium Channels: From Homeostasis to Neurodegeneration

Biomolecules ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1774
Author(s):  
Germana Cocozza ◽  
Stefano Garofalo ◽  
Riccardo Capitani ◽  
Giuseppina D’Alessandro ◽  
Cristina Limatola
Keyword(s):  
Potassium Channels ◽  
Neurodegenerative Diseases ◽  
Current Knowledge ◽  
Therapeutic Interventions ◽  
Cns Disorders ◽  
Pathological Conditions ◽  
Wide Range ◽  
Functional Features ◽  
Lateral Sclerosis

The growing interest in the role of microglia in the progression of many neurodegenerative diseases is developing in an ever-expedited manner, in part thanks to emergent new tools for studying the morphological and functional features of the CNS. The discovery of specific biomarkers of the microglia phenotype could find application in a wide range of human diseases, and creates opportunities for the discovery and development of tailored therapeutic interventions. Among these, recent studies highlight the pivotal role of the potassium channels in regulating microglial functions in physiological and pathological conditions such as Alzheimer’s Disease, Parkinson’s Disease, and Amyotrophic Lateral Sclerosis. In this review, we summarize the current knowledge of the involvement of the microglial potassium channels in several neurodegenerative diseases and their role as modulators of microglial homeostasis and dysfunction in CNS disorders.

scholarly journals Stress Granules and Neurodegenerative Disorders: A Scoping Review

2021 ◽  
Vol 13 ◽  
Author(s):  
Mohammad Reza Asadi ◽  
Marziyeh Sadat Moslehian ◽  
Hani Sabaie ◽  
Abbas Jalaiei ◽  
Soudeh Ghafouri-Fard ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Scoping Review ◽  
Neurodegenerative Disorders ◽  
Bioinformatics Analysis ◽  
Stress Granules ◽  
Inclusion Criteria ◽  
Frontotemporal Degeneration ◽  
Protein Components ◽  
Lateral Sclerosis

Cytoplasmic ribonucleoproteins called stress granules (SGs) are considered as one of the main cellular solutions against stress. Their temporary presence ends with stress relief. Any factor such as chronic stress or mutations in the structure of the components of SGs that lead to their permanent presence can affect their interactions with pathological aggregations and increase the degenerative effects. SGs involved in RNA mechanisms are important factors in the pathophysiology of neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS), frontotemporal degeneration (FTD), and Alzheimer's diseases (AD). Although many studies have been performed in the field of SGs and neurodegenerative disorders, so far, no systematic studies have been executed in this field. The purpose of this study is to provide a comprehensive perspective of all studies about the role of SGs in the pathogenesis of neurodegenerative disorders with a focus on the protein ingredients of these granules. This scoping review is based on a six-stage methodology structure and the PRISMA guideline. A systematic search of seven databases for qualified articles was conducted until December 2020. Publications were screened independently by two reviewers and quantitative and qualitative analysis was performed on the extracted data. Bioinformatics analysis was used to plot the network and predict interprotein interactions. In addition, GO analysis was performed. A total of 48 articles were identified that comply the inclusion criteria. Most studies on neurodegenerative diseases have been conducted on ALS, AD, and FTD using human post mortem tissues. Human derived cell line studies have been used only in ALS. A total 29 genes of protein components of SGs have been studied, the most important of which are TDP-43, TIA-1, PABP-1. Bioinformatics studies have predicted 15 proteins to interact with the protein components of SGs, which may be the constituents of SGs. Understanding the interactions between SGs and pathological aggregations in neurodegenerative diseases can provide new targets for treatment of these disorders.

scholarly journals Diagnostic and Therapeutic Potential of Exosomes in Neurodegenerative Diseases

2021 ◽  
Vol 13 ◽  
Author(s):  
Panyue Gao ◽  
Xinrong Li ◽  
Xinzhe Du ◽  
Sha Liu ◽  
Yong Xu
Keyword(s):  
Neurodegenerative Diseases ◽  
Neurodegenerative Disorders ◽  
Brain Function ◽  
Genetic Information ◽  
Therapeutic Potential ◽  
Early Biomarkers ◽  
Drug Molecules ◽  
The Brain ◽  
Lateral Sclerosis

Neurodegenerative diseases are closely related to brain function and the progression of the diseases are irreversible. Due to brain tissue being not easy to acquire, the study of the pathophysiology of neurodegenerative disorders has many limitations—lack of reliable early biomarkers and personalized treatment. At the same time, the blood-brain barrier (BBB) limits most of the drug molecules into the damaged areas of the brain, which makes a big drop in the effect of drug treatment. Exosomes, a kind of endogenous nanoscale vesicles, play a key role in cell signaling through the transmission of genetic information and proteins between cells. Because of the ability to cross the BBB, exosomes are expected to link peripheral changes to central nervous system (CNS) events as potential biomarkers, and can even be used as a therapeutic carrier to deliver molecules specifically to CNS. Here we summarize the role of exosomes in pathophysiology, diagnosis, prognosis, and treatment of some neurodegenerative diseases (Alzheimer’s Disease, Parkinson’s Disease, Huntington’s Disease, Amyotrophic Lateral Sclerosis).

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