scholarly journals Therapeutic Potential of α-Crystallins in Retinal Neurodegenerative Diseases

Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1001
Author(s):  
Ashutosh S. Phadte ◽  
Zachary B. Sluzala ◽  
Patrice E. Fort
Keyword(s):  
Cell Death ◽  
Animal Models ◽  
Neurodegenerative Diseases ◽  
Neurodegenerative Disease ◽  
Therapeutic Potential ◽  
Loss Of Function ◽  
Neuronal Viability ◽  
Current Review ◽  
Progressive Loss ◽  
Apoptotic Activity

The chaperone and anti-apoptotic activity of α-crystallins (αA- and αB-) and their derivatives has received increasing attention due to their tremendous potential in preventing cell death. While originally known and described for their role in the lens, the upregulation of these proteins in cells and animal models of neurodegenerative diseases highlighted their involvement in adaptive protective responses to neurodegeneration associated stress. However, several studies also suggest that chronic neurodegenerative conditions are associated with progressive loss of function of these proteins. Thus, while external supplementation of α-crystallin shows promise, their potential as a protein-based therapeutic for the treatment of chronic neurodegenerative diseases remains ambiguous. The current review aims at assessing the current literature supporting the anti-apoptotic potential of αA- and αB-crystallins and its potential involvement in retinal neurodegenerative diseases. The review further extends into potentially modulating the chaperone and the anti-apoptotic function of α-crystallins and the use of such functionally enhanced proteins for promoting neuronal viability in retinal neurodegenerative disease.

scholarly journals Contribution of rare variant associations to neurodegenerative disease presentation

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Allison A. Dilliott ◽  
Abdalla Abdelhady ◽  
Kelly M. Sunderland ◽  
Sali M. K. Farhan ◽  
Agessandro Abrahao ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Neurodegenerative Disease ◽  
Rare Variant ◽  
Genetic Factors ◽  
Association Studies ◽  
Loss Of Function ◽  
Phenotypic Effect ◽  
Association Analyses ◽  
Individual Gene ◽  
Genetic Overlap

AbstractGenetic factors contribute to neurodegenerative diseases, with high heritability estimates across diagnoses; however, a large portion of the genetic influence remains poorly understood. Many previous studies have attempted to fill the gaps by performing linkage analyses and association studies in individual disease cohorts, but have failed to consider the clinical and pathological overlap observed across neurodegenerative diseases and the potential for genetic overlap between the phenotypes. Here, we leveraged rare variant association analyses (RVAAs) to elucidate the genetic overlap among multiple neurodegenerative diagnoses, including Alzheimer’s disease, amyotrophic lateral sclerosis, frontotemporal dementia (FTD), mild cognitive impairment, and Parkinson’s disease (PD), as well as cerebrovascular disease, using the data generated with a custom-designed neurodegenerative disease gene panel in the Ontario Neurodegenerative Disease Research Initiative (ONDRI). As expected, only ~3% of ONDRI participants harboured a monogenic variant likely driving their disease presentation. Yet, when genes were binned based on previous disease associations, we observed an enrichment of putative loss of function variants in PD genes across all ONDRI cohorts. Further, individual gene-based RVAA identified significant enrichment of rare, nonsynonymous variants in PARK2 in the FTD cohort, and in NOTCH3 in the PD cohort. The results indicate that there may be greater heterogeneity in the genetic factors contributing to neurodegeneration than previously appreciated. Although the mechanisms by which these genes contribute to disease presentation must be further explored, we hypothesize they may be a result of rare variants of moderate phenotypic effect contributing to overlapping pathology and clinical features observed across neurodegenerative diagnoses.

scholarly journals Natural Products and Their Bioactive Compounds: Neuroprotective Potentials against Neurodegenerative Diseases

2020 ◽  
Vol 2020 ◽  
pp. 1-30 ◽  
Author(s):  
Nur Shafika Mohd Sairazi ◽  
K. N. S. Sirajudeen
Keyword(s):  
Cell Death ◽  
Natural Products ◽  
Neurodegenerative Diseases ◽  
Bioactive Compounds ◽  
Therapeutic Potential ◽  
Neuroprotective Effect ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Neuronal Structure ◽  
And Function

In recent years, natural products, which originate from plants, animals, and fungi, together with their bioactive compounds have been intensively explored and studied for their therapeutic potentials for various diseases such as cardiovascular, diabetes, hypertension, reproductive, cancer, and neurodegenerative diseases. Neurodegenerative diseases, including Alzheimer’s disease, Huntington’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis are characterized by the progressive dysfunction and loss of neuronal structure and function that resulted in the neuronal cell death. Since the multifactorial pathological mechanisms are associated with neurodegeneration, targeting multiple mechanisms of actions and neuroprotection approach, which involves preventing cell death and restoring the function to damaged neurons, could be promising strategies for the prevention and therapeutic of neurodegenerative diseases. Natural products have emerged as potential neuroprotective agents for the treatment of neurodegenerative diseases. This review focused on the therapeutic potential of natural products and their bioactive compounds to exert a neuroprotective effect on the pathologies of neurodegenerative diseases.

scholarly journals Screening Pesticides for Neuropathogenicity

2006 ◽  
Vol 2006 ◽  
pp. 1-13 ◽  
Author(s):  
John D. Doherty
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Animal Models ◽  
Neurodegenerative Diseases ◽  
Neurodegenerative Disease ◽  
Laboratory Animals ◽  
The Public ◽  
Delayed Neuropathy ◽  
Time Of Administration ◽  
Human Neurodegenerative Disease

Pesticides are routinely screened in studies that follow specific guidelines for possible neuropathogenicity in laboratory animals. These tests will detect chemicals that are by themselves strong inducers of neuropathogenesis if the tested strain is susceptible relative to the time of administration and methodology of assessment. Organophosphate induced delayed neuropathy (OPIDN) is the only known human neurodegenerative disease associated with pesticides and the existing study guidelines with hens are a standard for predicting the potential for organophosphates to cause OPIDN. Although recent data have led to the suggestion that pesticides may be risk factors for Parkinsonism syndrome, there are no specific protocols to evaluate this syndrome in the existing study guidelines. Ideally additional animal models for human neurodegenerative diseases need to be developed and incorporated into the guidelines to further assure the public that limited exposure to pesticides is not a risk factor for neurodegenerative diseases.

scholarly journals Parkinson’s Disease and Autophagy

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Ana María Sánchez-Pérez ◽  
Berta Claramonte-Clausell ◽  
Juan Vicente Sánchez-Andrés ◽  
María Trinidad Herrero
Keyword(s):  
Cell Death ◽  
Animal Models ◽  
Neurodegenerative Disease ◽  
Causal Relationship ◽  
Neurodegenerative Disorders ◽  
Therapeutic Strategy ◽  
Neuroprotective Effects ◽  
Autophagy Induction ◽  
Effective Therapeutic Strategy ◽  
The Brain

It is generally accepted that a correlation between neurodegenerative disease and protein aggregation in the brain exists; however, a causal relationship has not been elucidated. In neurons, failure of autophagy may result in the accumulation of aggregate-prone proteins and subsequent neurodegeneration. Thus, pharmacological induction of autophagy to enhance the clearance of intracytoplasmic aggregate-prone proteins has been considered as a therapeutic strategy to ameliorate pathology in cell and animal models of neurodegenerative disorders. However, autophagy has also been found to be a factor in the onset of these diseases, which raises the question of whether autophagy induction is an effective therapeutic strategy, or, on the contrary, can result in cell death. In this paper, we will first describe the autophagic machinery, and we will consider the literature to discuss the neuroprotective effects of autophagy.

scholarly journals Mitochondrial Dynamics: A Key Role in Neurodegeneration and a Potential Target for Neurodegenerative Disease

2021 ◽  
Vol 15 ◽  
Author(s):  
Danying Yang ◽  
Jun Ying ◽  
Xifeng Wang ◽  
Tiancheng Zhao ◽  
Sungtae Yoon ◽  
...  
Keyword(s):  
Cell Death ◽  
Neurodegenerative Diseases ◽  
Neurodegenerative Disease ◽  
Significant Influence ◽  
Mitochondrial Dynamics ◽  
Therapeutic Strategies ◽  
Pathological Process ◽  
Mitochondrial Functions ◽  
Associated Proteins

In neurodegenerative diseases, neurodegeneration has been related to several mitochondrial dynamics imbalances such as excessive fragmentation of mitochondria, impaired mitophagy, and blocked mitochondria mitochondrial transport in axons. Mitochondria are dynamic organelles, and essential for energy conversion, neuron survival, and cell death. As mitochondrial dynamics have a significant influence on homeostasis, in this review, we mainly discuss the role of mitochondrial dynamics in several neurodegenerative diseases. There is evidence that several mitochondrial dynamics-associated proteins, as well as related pathways, have roles in the pathological process of neurodegenerative diseases with an impact on mitochondrial functions and metabolism. However, specific pathological mechanisms need to be better understood in order to propose new therapeutic strategies targeting mitochondrial dynamics that have shown promise in recent studies.

scholarly journals Glaucoma and Antioxidants: Review and Update

Antioxidants ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 1031 ◽  
Author(s):  
Jose Javier Garcia-Medina ◽  
Elena Rubio-Velazquez ◽  
Maria Dolores Lopez-Bernal ◽  
Alejandro Cobo-Martinez ◽  
Vicente Zanon-Moreno ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Clinical Trials ◽  
Cell Death ◽  
Animal Models ◽  
Neurodegenerative Disease ◽  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Retinal Ganglion ◽  
Progressive Degeneration ◽  
Deleterious Consequence

Glaucoma is a neurodegenerative disease characterised by the progressive degeneration of retinal ganglion cells. Oxidative stress has been related to the cell death in this disease. Theoretically, this deleterious consequence can be reduced by antioxidants substances. The aim of this review is to assemble the studies published in relation to antioxidant supplementation and its effects on glaucoma and to offer the reader an update on this field. With this purpose, we have included studies in animal models of glaucoma and clinical trials. Although there are variable results, supplementation with antioxidants in glaucoma may be a promising therapy in glaucoma.

scholarly journals Induced Pluripotent Stem Cell (iPSC)-Based Neurodegenerative Disease Models for Phenotype Recapitulation and Drug Screening

Molecules ◽  
2020 ◽  
Vol 25 (8) ◽  
pp. 2000 ◽  
Author(s):  
Chia-Yu Chang ◽  
Hsiao-Chien Ting ◽  
Ching-Ann Liu ◽  
Hong-Lin Su ◽  
Tzyy-Wen Chiou ◽  
...  
Keyword(s):  
Animal Models ◽  
Neurodegenerative Diseases ◽  
Neurodegenerative Disease ◽  
Drug Screening ◽  
Large Scale ◽  
Small Animal ◽  
Induced Pluripotent Stem Cell ◽  
Disease Models ◽  
Therapeutic Drugs ◽  
Induced Pluripotent

Neurodegenerative diseases represent a significant unmet medical need in our aging society. There are no effective treatments for most of these diseases, and we know comparatively little regarding pathogenic mechanisms. Among the challenges faced by those involved in developing therapeutic drugs for neurodegenerative diseases, the syndromes are often complex, and small animal models do not fully recapitulate the unique features of the human nervous system. Human induced pluripotent stem cells (iPSCs) are a novel technology that ideally would permit us to generate neuronal cells from individual patients, thereby eliminating the problem of species-specificity inherent when using animal models. Specific phenotypes of iPSC-derived cells may permit researchers to identify sub-types and to distinguish among unique clusters and groups. Recently, iPSCs were used for drug screening and testing for neurologic disorders including Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), spinocerebellar atrophy (SCA), and Zika virus infection. However, there remain many challenges still ahead, including how one might effectively recapitulate sporadic disease phenotypes and the selection of ideal phenotypes and for large-scale drug screening. Fortunately, quite a few novel strategies have been developed that might be combined with an iPSC-based model to solve these challenges, including organoid technology, single-cell RNA sequencing, genome editing, and deep learning artificial intelligence. Here, we will review current applications and potential future directions for iPSC-based neurodegenerative disease models for critical drug screening.

scholarly journals Zebrafish and Medaka: Important Animal Models for Human Neurodegenerative Diseases

2021 ◽  
Vol 22 (19) ◽  
pp. 10766
Author(s):  
Jing Wang ◽  
Hong Cao
Keyword(s):  
Animal Models ◽  
Neurodegenerative Diseases ◽  
Neurodegenerative Disease ◽  
Large Scale ◽  
Gene Knockout ◽  
Forward Genetics ◽  
Suitable Model ◽  
Human Beings ◽  
Fast Development ◽  
Human Neurodegenerative Disease

Animal models of human neurodegenerative disease have been investigated for several decades. In recent years, zebrafish (Danio rerio) and medaka (Oryzias latipes) have become popular in pathogenic and therapeutic studies about human neurodegenerative diseases due to their small size, the optical clarity of embryos, their fast development, and their suitability to large-scale therapeutic screening. Following the emergence of a new generation of molecular biological technologies such as reverse and forward genetics, morpholino, transgenesis, and gene knockout, many human neurodegenerative disease models, such as Parkinson’s, Huntington’s, and Alzheimer’s, were constructed in zebrafish and medaka. These studies proved that zebrafish and medaka genes are functionally conserved in relation to their human homologues, so they exhibit similar neurodegenerative phenotypes to human beings. Therefore, fish are a suitable model for the investigation of pathologic mechanisms of neurodegenerative diseases and for the large-scale screening of drugs for potential therapy. In this review, we summarize the studies in modelling human neurodegenerative diseases in zebrafish and medaka in recent years.

Involvement of Heme Oxygenase-1 in Neuropsychiatric and Neurodegenerative Diseases

2018 ◽  
Vol 24 (20) ◽  
pp. 2283-2302 ◽  
Author(s):  
Vivian B. Neis ◽  
Priscila B. Rosa ◽  
Morgana Moretti ◽  
Ana Lucia S. Rodrigues
Keyword(s):  
Neurodegenerative Diseases ◽  
Heme Oxygenase ◽  
Therapeutic Potential ◽  
Redox Homeostasis ◽  
Antioxidant Defenses ◽  
Heme Oxygenase 1 ◽  
Physiological Conditions ◽  
And Oxidative Stress ◽  
Defensive Mechanism

Heme oxygenase (HO) family catalyzes the conversion of heme into free iron, carbon monoxide and biliverdin. It possesses two well-characterized isoforms: HO-1 and HO-2. Under brain physiological conditions, the expression of HO-2 is constitutive, abundant and ubiquitous, whereas HO-1 mRNA and protein are restricted to small populations of neurons and neuroglia. HO-1 is an inducible enzyme that has been shown to participate as an essential defensive mechanism for neurons exposed to oxidant challenges, being related to antioxidant defenses in certain neuropathological conditions. Considering that neurodegenerative diseases (Alzheimer’s Disease (AD), Parkinson’s Disease (PD) and Multiple Sclerosis (MS)) and neuropsychiatric disorders (depression, anxiety, Bipolar Disorder (BD) and schizophrenia) are associated with increased inflammatory markers, impaired redox homeostasis and oxidative stress, conditions that may be associated with alterations in HO-levels/activity, the purpose of this review is to present evidence on the possible role of HO-1 in these Central Nervous System (CNS) diseases. In addition, the possible therapeutic potential of targeting brain HO-1 is explored in this review.

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