scholarly journals Novel Approaches for the Treatment of Alzheimer’s and Parkinson’s Disease

2019 ◽  
Vol 20 (3) ◽  
pp. 719 ◽  
Author(s):  
Michiel Van Bulck ◽  
Ana Sierra-Magro ◽  
Jesus Alarcon-Gil ◽  
Ana Perez-Castillo ◽  
Jose Morales-Garcia
Keyword(s):  
Neurodegenerative Diseases ◽  
Neurodegenerative Disorders ◽  
Current Knowledge ◽  
Chronic Illnesses ◽  
Aging Brain ◽  
Therapeutic Approaches ◽  
Neurodegenerative Process ◽  
Age Related ◽  
Parkinson’S Diseases ◽  
Current Therapies

Neurodegenerative disorders affect around one billion people worldwide. They can arise from a combination of genomic, epigenomic, metabolic, and environmental factors. Aging is the leading risk factor for most chronic illnesses of old age, including Alzheimer’s and Parkinson’s diseases. A progressive neurodegenerative process and neuroinflammation occur, and no current therapies can prevent, slow, or halt disease progression. To date, no novel disease-modifying therapies have been shown to provide significant benefit for patients who suffer from these devastating disorders. Therefore, early diagnosis and the discovery of new targets and novel therapies are of upmost importance. Neurodegenerative diseases, like in other age-related disorders, the progression of pathology begins many years before the onset of symptoms. Many efforts in this field have led to the conclusion that exits some similar events among these diseases that can explain why the aging brain is so vulnerable to suffer neurodegenerative diseases. This article reviews the current knowledge about these diseases by summarizing the most common features of major neurodegenerative disorders, their causes and consequences, and the proposed novel therapeutic approaches.

The effects of aging, injury and disease on microglial function: a case for cellular senescence

2007 ◽  
Vol 3 (3) ◽  
pp. 245-253 ◽  
Author(s):  
Kelly R. Miller ◽  
Wolfgang J. Streit
Keyword(s):  
Neurodegenerative Diseases ◽  
Cellular Senescence ◽  
Current Knowledge ◽  
Treatment Strategies ◽  
Aging Brain ◽  
Normal Brain ◽  
Age Related ◽  
Anti Inflammatory ◽  
Effects Of Aging ◽  
And Function

AbstractNeuroinflammation resulting from chronic reactive microgliosis is thought to contribute to age-related neurodegeneration, as well as age-related neurodegenerative diseases, specifically Alzheimer's disease (AD). Support of this theory comes from studies reporting a progressive, age-associated increase in microglia with an activated phenotype. Although the underlying cause(s) of this microglial reactivity is idiopathic, an accepted therapeutic strategy for the treatment of AD is inhibition of microglial activation using anti-inflammatory agents. Although the effectiveness of anti-inflammatory treatment for AD remains equivocal, microglial inhibition is being tested as a potential treatment for additional neurodegenerative disorders including amyotrophic lateral sclerosis and Parkinson's disease. Given the important and necessary functions of microglia in normal brain, careful evaluation of microglial function in the aged brain is a necessary first step in targeting more precise treatment strategies for aging-related neurodegenerative diseases. Studies from our laboratory have shown multiple age-related changes in microglial morphology and function that are suggestive of cellular senescence. In this manuscript, we review current knowledge of microglia in the aging brain and present new, unpublished work that further supports the theory that microglia experience an age-related decline in proliferative function as a result of cellular senescence.

scholarly journals The Biology and Pathobiology of Glutamatergic, Cholinergic, and Dopaminergic Signaling in the Aging Brain

2021 ◽  
Vol 13 ◽  
Author(s):  
Anna Gasiorowska ◽  
Malgorzata Wydrych ◽  
Patrycja Drapich ◽  
Maciej Zadrozny ◽  
Marta Steczkowska ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Experimental Studies ◽  
Significant Risk ◽  
Significant Risk Factor ◽  
The Elderly ◽  
Aging Brain ◽  
Detailed Knowledge ◽  
Age Related ◽  
Parkinson’S Diseases ◽  
The Brain

The elderly population is growing worldwide, with important health and socioeconomic implications. Clinical and experimental studies on aging have uncovered numerous changes in the brain, such as decreased neurogenesis, increased synaptic defects, greater metabolic stress, and enhanced inflammation. These changes are associated with cognitive decline and neurobehavioral deficits. Although aging is not a disease, it is a significant risk factor for functional worsening, affective impairment, disease exaggeration, dementia, and general disease susceptibility. Conversely, life events related to mental stress and trauma can also lead to accelerated age-associated disorders and dementia. Here, we review human studies and studies on mice and rats, such as those modeling human neurodegenerative diseases, that have helped elucidate (1) the dynamics and mechanisms underlying the biological and pathological aging of the main projecting systems in the brain (glutamatergic, cholinergic, and dopaminergic) and (2) the effect of defective glutamatergic, cholinergic, and dopaminergic projection on disabilities associated with aging and neurodegenerative disorders, such as Alzheimer’s and Parkinson’s diseases. Detailed knowledge of the mechanisms of age-related diseases can be an important element in the development of effective ways of treatment. In this context, we briefly analyze which adverse changes associated with neurodegenerative diseases in the cholinergic, glutaminergic and dopaminergic systems could be targeted by therapeutic strategies developed as a result of our better understanding of these damaging mechanisms.

scholarly journals Peroxiredoxins in Neurodegenerative Diseases

Antioxidants ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 1203
Author(s):  
Monika Szeliga
Keyword(s):  
Neurodegenerative Diseases ◽  
Neurodegenerative Disorders ◽  
Nitrosative Stress ◽  
Current Knowledge ◽  
Lewy Bodies ◽  
Substantial Evidence ◽  
Defense Systems ◽  
Neurodegenerative Process ◽  
Antioxidant Mechanisms ◽  
Lateral Sclerosis

Substantial evidence indicates that oxidative/nitrosative stress contributes to the neurodegenerative diseases. Peroxiredoxins (PRDXs) are one of the enzymatic antioxidant mechanisms neutralizing reactive oxygen/nitrogen species. Since mammalian PRDXs were identified 30 years ago, their significance was long overshadowed by the other well-studied ROS/RNS defense systems. An increasing number of studies suggests that these enzymes may be involved in the neurodegenerative process. This article reviews the current knowledge on the expression and putative roles of PRDXs in neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease and dementia with Lewy bodies, multiple sclerosis, amyotrophic lateral sclerosis and Huntington’s disease.

scholarly journals Two human metabolites rescue a C. elegans model of Alzheimer’s disease via a cytosolic unfolded protein response

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Priyanka Joshi ◽  
Michele Perni ◽  
Ryan Limbocker ◽  
Benedetta Mannini ◽  
Sam Casford ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Unfolded Protein Response ◽  
Neurodegenerative Disorders ◽  
C Elegans ◽  
Unfolded Protein ◽  
Model Of Alzheimer’S Disease ◽  
Age Related ◽  
Parkinson’S Diseases ◽  
Protein Response

AbstractAge-related changes in cellular metabolism can affect brain homeostasis, creating conditions that are permissive to the onset and progression of neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases. Although the roles of metabolites have been extensively studied with regard to cellular signaling pathways, their effects on protein aggregation remain relatively unexplored. By computationally analysing the Human Metabolome Database, we identified two endogenous metabolites, carnosine and kynurenic acid, that inhibit the aggregation of the amyloid beta peptide (Aβ) and rescue a C. elegans model of Alzheimer’s disease. We found that these metabolites act by triggering a cytosolic unfolded protein response through the transcription factor HSF-1 and downstream chaperones HSP40/J-proteins DNJ-12 and DNJ-19. These results help rationalise previous observations regarding the possible anti-ageing benefits of these metabolites by providing a mechanism for their action. Taken together, our findings provide a link between metabolite homeostasis and protein homeostasis, which could inspire preventative interventions against neurodegenerative disorders.

Multitarget therapeutic approaches for Alzheimer's and Parkinson's diseases: an opportunity or an illusion?

2021 ◽  
Author(s):  
Maria João Matos
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Diseases ◽  
Therapeutic Options ◽  
Therapeutic Approaches ◽  
Recent Information ◽  
Temporary Relief ◽  
Parkinson’S Diseases ◽  
Innovative Approaches

Alzheimer's and Parkinson's disease are the most prevalent neurodegenerative diseases and the leading causes of dementia worldwide. The etiology of these multifactorial pathologies is not completely known. The available therapeutic approaches can cause temporary relief of symptoms but cannot slow down their progression or cure them. Life-changing therapeutic solutions are urgently needed, as the number of people suffering from these pathologies has been increasing quickly over the last few decades. Several targets are being studied, and innovative approaches are being pursued to find new therapeutic options. This overview is focused on the most recent information regarding the paradigm of using multitarget compounds to treat both Alzheimer's and Parkinson's disease.

Immunotherapy for Neurodegenerative Disorders

2016 ◽  
Author(s):  
David Morgan
Keyword(s):  
At Risk ◽  
Neurodegenerative Diseases ◽  
Neurodegenerative Disease ◽  
Neurodegenerative Disorders ◽  
Health Concern ◽  
Cultured Neurons ◽  
Preclinical Data ◽  
Age Related ◽  
The World ◽  
Disease Modifying

Neurodegenerative diseases are a growing health concern through the world as gains in longevity result in an increased population at risk of these age-related disorders. Unfortunately no disease modifying treatments exist for these disorders. Over the last three decades enormous insights have been gained into the causes of these disorders. One approach to treating these diseases is to direct immunotherapy against the misfolded proteins that accumulate within the brains of those with neurodegenerative disease in an attempt to clear the accumulating proteins and slow or prevent expression of the disease. This chapter summarizes the recent (and frustrating) experience with anti-Aβ‎ immunotherapy to treat mild to moderate Alzheimer’s disease, and holds hope that newer generation antibodies and treating presymptomatic disease will have greater impact. In addition, it reviews the preclinical data regarding approaches to treating tau, synuclein, and prion disorders, all of which demonstrate consistent effects in mice and cultured neurons.

scholarly journals Mitochondrial dysfunctions and neurodegenerative diseases: a mini-review

2021 ◽  
Vol 10 (4) ◽  
pp. 147-149
Author(s):  
Ratan Kumari ◽  
Nikhila Shekhar ◽  
Sakshi Tyagi ◽  
Ajit Kumar Thakur
Keyword(s):  
Reactive Oxygen Species ◽  
Neurodegenerative Diseases ◽  
Mitochondrial Dysfunction ◽  
Neurodegenerative Disorders ◽  
Oxygen Species ◽  
Primary Reason ◽  
Mitochondrial Dysfunctions ◽  
Detailed Understanding ◽  
Age Related ◽  
Different Types

Mitochondrial dysfunction is estimated to be the primary reason involved in different types of neurodegenerative disorders as mitochondria is suggested to be important in the production of reactive oxygen species. Recently, several evidences have emerged out for impaired mitochondrial structures and functions viz. shape, size, fission-fusion, distribution, movement etc. in neurodegenerative diseases especially with Alzheimer’s disease, Parkinson’s disease and Huntington’s disease. Therefore, apart from looking neurodegenerative diseases on the whole, a detailed understanding of the functioning of mitochondria and their role in degeneration would pave new options for the therapy of age-related neurodegenerative diseases.

scholarly journals The Interplay of the Unfolded Protein Response in Neurodegenerative Diseases: A Therapeutic Role of Curcumin

2021 ◽  
Vol 13 ◽  
Author(s):  
Sitabja Mukherjee ◽  
Awdhesh Kumar Mishra ◽  
G. D. Ghouse Peer ◽  
Sali Abubaker Bagabir ◽  
Shafiul Haque ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Neurodegenerative Diseases ◽  
Unfolded Protein Response ◽  
Neurodegenerative Disorders ◽  
The Body ◽  
Model Systems ◽  
Unfolded Protein ◽  
Body Tissues ◽  
Parkinson’S Diseases ◽  
Protein Response

Abnormal accumulation of misfolded proteins in the endoplasmic reticulum and their aggregation causes inflammation and endoplasmic reticulum stress. This promotes accumulation of toxic proteins in the body tissues especially brain leading to manifestation of neurodegenerative diseases. The studies suggest that deregulation of proteostasis, particularly aberrant unfolded protein response (UPR) signaling, may be a common morbific process in the development of neurodegeneration. Curcumin, the mixture of low molecular weight polyphenolic compounds from turmeric, Curcuma longa has shown promising response to prevents many diseases including current global severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and neurodegenerative disorders. The UPR which correlates positively with neurodegenerative disorders were found affected by curcumin. In this review, we examine the evidence from many model systems illustrating how curcumin interacts with UPR and slows down the development of various neurodegenerative disorders (ND), e.g., Alzheimer’s and Parkinson’s diseases. The recent global increase in ND patients indicates that researchers and practitioners will need to develop a new pharmacological drug or treatment to manage and cure these neurodegenerative diseases.

Sleep disorders in neurodegenerative diseases other than Parkinson disease and multiple system atrophy

2017 ◽  
Author(s):  
Raffaele Manni ◽  
Michele Terzaghi
Keyword(s):  
Neurodegenerative Diseases ◽  
Sleep Disorders ◽  
Neurodegenerative Disorders ◽  
Sleep Problems ◽  
Lewy Bodies ◽  
Corticobasal Degeneration ◽  
Spinocerebellar Ataxias ◽  
Age Related ◽  
Key Points ◽  
Sleep Alterations

This chapter examines sleep–wake disturbances occurring in the most common neurodegenerative disorders. It reviews sleep alterations in Alzheimer disease and dementia with Lewy bodies. It also discusses sleep problems in progressive supranuclear palsy, corticobasal degeneration, Huntington disease, and spinocerebellar ataxias. Status dissociatus as an extreme form of sleep alteration in advanced neurodegenerative diseases is also considered. The chapter reviews the key points for the treatment of disrupted sleep in neurodegenerative disorders, with a focus on pharmacological and nonpharmacological interventions to improve sleep continuity. It also summarizes paraphysiological age-related changes in sleep patterns and discusses indications and procedures for clinical and instrumental assessment of sleep disorders in neurodegenerative disorders.

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.

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