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American Family Physician Apr 1999Parkinson's disease is a progressive degenerative disorder of the central nervous system. The hallmark physical signs are tremor, rigidity and bradykinesia. Idiopathic... (Review)
Review
Parkinson's disease is a progressive degenerative disorder of the central nervous system. The hallmark physical signs are tremor, rigidity and bradykinesia. Idiopathic Parkinson's disease is caused by the progressive loss of dopaminergic neurons in the substantia nigra and nigrostriatal pathway of the midbrain. Secondary parkinsonism may be caused by certain drugs (e.g., metoclopramide and haloperidol) or by cerebrovascular disease (e.g., multiple lacunar strokes). The disease can usually be diagnosed based on the history and physical findings. Dopamine replacement is still considered the most efficacious treatment for Parkinson's disease, but dopamine agonists, formerly prescribed only as adjunctive therapy, are emerging as useful initial therapy. Other pharmacologic treatments include drugs that inhibit dopamine-metabolizing enzymes (monoamine oxidase-B and catechol O-methyltransferase). Injections of botulinum toxin can be helpful in patients with associated dystonia or blepharospasm. Surgery may be indicated for certain patients or when symptoms do not respond to medical therapy. Additional adjunctive therapies include physical therapy, nutritional counseling and techniques to help patients manage emotional and cognitive changes related to the disease.
Topics: Antiparkinson Agents; Humans; Internet; Neurosurgical Procedures; Parkinson Disease, Secondary; Patient Education as Topic; Self-Help Groups; Teaching Materials
PubMed: 10221302
DOI: No ID Found -
Journal of Alzheimer's Disease : JAD 2018Neurodegeneration is defined as the progressive loss of structure or function of the neurons. As the nature of degenerative cell loss is currently not clear, there is no... (Review)
Review
Neurodegeneration is defined as the progressive loss of structure or function of the neurons. As the nature of degenerative cell loss is currently not clear, there is no specific molecular marker to measure neurodegeneration. Therefore, researchers have been using apoptotic markers to measure neurodegeneration. However, neurodegeneration is completely different from apoptosis by morphology and time course. Lacking specific molecular marker has been the major hindrance in research of neurodegenerative disorders. Alzheimer's disease (AD) is the most common neurodegenerative disorder, and tau accumulation forming neurofibrillary tangles is a hallmark pathology in the AD brains, suggesting that tau must play a critical role in AD neurodegeneration. Here we review part of our published papers on tau-related studies, and share our thoughts on the nature of tau-associated neurodegeneration in AD.
Topics: Animals; Humans; Nerve Degeneration; Neurodegenerative Diseases; tau Proteins
PubMed: 29562535
DOI: 10.3233/JAD-170788 -
Nature Reviews. Genetics Oct 2012There has been mounting evidence of a causal role for telomere dysfunction in a number of degenerative disorders. Their manifestations encompass common disease states... (Review)
Review
There has been mounting evidence of a causal role for telomere dysfunction in a number of degenerative disorders. Their manifestations encompass common disease states such as idiopathic pulmonary fibrosis and bone marrow failure. Although these disorders seem to be clinically diverse, collectively they comprise a single syndrome spectrum defined by the short telomere defect. Here we review the manifestations and unique genetics of telomere syndromes. We also discuss their underlying molecular mechanisms and significance for understanding common age-related disease processes.
Topics: Animals; Genetic Association Studies; Genetic Diseases, Inborn; Genetic Predisposition to Disease; Humans; Models, Biological; Quantitative Trait, Heritable; Syndrome; Telomere
PubMed: 22965356
DOI: 10.1038/nrg3246 -
Antioxidants (Basel, Switzerland) Feb 2019Longevity is determined by a number of factors, including genetic, environmental and lifestyle factors. A major factor affecting longevity is the development of... (Review)
Review
Longevity is determined by a number of factors, including genetic, environmental and lifestyle factors. A major factor affecting longevity is the development of degenerative disorders such as cardiovascular disease, diabetes, kidney disease and liver disease, particularly where these occur as co-morbidities. In this article, we review the potential role of supplementation with coenzyme Q10 (CoQ10) for the prevention or management of these disorders. Thus, randomised controlled clinical trials have shown supplementation with CoQ10 or CoQ10 plus selenium reduces mortality by approximately 50% in patients with cardiovascular disease, or in the normal elderly population, respectively. Similarly, CoQ10 supplementation improves glycaemic control and vascular dysfunction in type II diabetes, improves renal function in patients with chronic kidney disease, and reduces liver inflammation in patients with non-alcoholic fatty liver disease. The beneficial role of supplemental CoQ10 in the above disorders is considered to result from a combination of its roles in cellular energy generation, as an antioxidant and as an anti-inflammatory agent.
PubMed: 30781472
DOI: 10.3390/antiox8020044 -
Molecular Genetics and Metabolism Aug 2016The mucopolysaccharidoses (MPS) are a family of lysosomal storage disorders characterized by deficient activity of enzymes that degrade glycosaminoglycans (GAGs).... (Review)
Review
The mucopolysaccharidoses (MPS) are a family of lysosomal storage disorders characterized by deficient activity of enzymes that degrade glycosaminoglycans (GAGs). Skeletal disease is common in MPS patients, with the severity varying both within and between subtypes. Within the spectrum of skeletal disease, spinal manifestations are particularly prevalent. Developmental and degenerative abnormalities affecting the substructures of the spine can result in compression of the spinal cord and associated neural elements. Resulting neurological complications, including pain and paralysis, significantly reduce patient quality of life and life expectancy. Systemic therapies for MPS, such as hematopoietic stem cell transplantation and enzyme replacement therapy, have shown limited efficacy for improving spinal manifestations in patients and animal models. Therefore, there is a pressing need for new therapeutic approaches that specifically target this debilitating aspect of the disease. In this review, we examine how pathological abnormalities affecting the key substructures of the spine - the discs, vertebrae, odontoid process and dura - contribute to the progression of spinal deformity and symptomatic compression of neural elements. Specifically, we review current understanding of the underlying pathophysiology of spine disease in MPS, how the tissues of the spine respond to current clinical and experimental treatments, and discuss future strategies for improving the efficacy of these treatments.
Topics: Enzyme Replacement Therapy; Glycosaminoglycans; Humans; Mucopolysaccharidoses; Quality of Life; Spinal Diseases; Spine
PubMed: 27296532
DOI: 10.1016/j.ymgme.2016.06.002 -
Neuroscience Letters Jun 2019Behavioral and Psychological Symptoms of Dementia (BPSD), present in almost 90% of patients with Alzheimer's Disease (AD), cause extensive impairment leading to reduced... (Review)
Review
Behavioral and Psychological Symptoms of Dementia (BPSD), present in almost 90% of patients with Alzheimer's Disease (AD), cause extensive impairment leading to reduced independence and inability to complete activities of daily living. Though BPSD includes a wide range of symptoms, such as agitation, aggression, disinhibition, anxiety, depression, apathy, delusions, and hallucinations. Certain BPSD in AD co-present and can be clustered into distinct domains based on their frequency of co-occurrence. As these BPSD are so pervasive in any stages of AD, the disease may be better characterized as a disorder of heterogeneous degenerative symptoms across a number of symptom domains, with the most prominent domain comprising memory and cognitive deficits. Importantly, there are no FDA-approved drugs to treat these BPSD, and new approaches must be considered to develop effective treatments for AD patients. The biogenic monoamine 5-hydroxytryptamine (5-HT), or serotonin, works as both a neurotransmitter and neuromodulator, which has been tied to cognitive decline and multiple BPSD domains. This review summarizes the evidence for specific serotonergic system alterations across some of the well-studied cognitive, behavioral, and psychiatric domains. Though differences in overall serotonergic transmission occur in AD, circuit-specific alterations in individual 5-HT receptors (5-HTRs) are likely linked to the heterogeneous presentation of BPSD in AD.
Topics: Alzheimer Disease; Animals; Cognition; Humans; Memory; Mood Disorders; Psychotic Disorders; Receptors, Serotonin; Serotonin
PubMed: 30946928
DOI: 10.1016/j.neulet.2019.03.050 -
Cells Jan 2021The activity of the mitochondrial permeability transition pore, mPTP, a highly regulated multi-component mega-channel, is enhanced in aging and in aging-driven... (Review)
Review
The activity of the mitochondrial permeability transition pore, mPTP, a highly regulated multi-component mega-channel, is enhanced in aging and in aging-driven degenerative diseases. mPTP activity accelerates aging by releasing large amounts of cell-damaging reactive oxygen species, Ca and NAD. The various pathways that control the channel activity, directly or indirectly, can therefore either inhibit or accelerate aging or retard or enhance the progression of aging-driven degenerative diseases and determine lifespan and healthspan. Autophagy, a catabolic process that removes and digests damaged proteins and organelles, protects the cell against aging and disease. However, the protective effect of autophagy depends on mTORC2/SKG1 inhibition of mPTP. Autophagy is inhibited in aging cells. Mitophagy, a specialized form of autophagy, which retards aging by removing mitochondrial fragments with activated mPTP, is also inhibited in aging cells, and this inhibition leads to increased mPTP activation, which is a major contributor to neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases. The increased activity of mPTP in aging turns autophagy/mitophagy into a destructive process leading to cell aging and death. Several drugs and lifestyle modifications that enhance healthspan and lifespan enhance autophagy and inhibit the activation of mPTP. Therefore, elucidating the intricate connections between pathways that activate and inhibit mPTP, in the context of aging and degenerative diseases, could enhance the discovery of new drugs and lifestyle modifications that slow aging and degenerative disease.
Topics: Animals; Autophagy; Disease; Humans; Longevity; Mitochondrial Permeability Transition Pore; Mitophagy; Models, Biological
PubMed: 33418876
DOI: 10.3390/cells10010079 -
CNS & Neurological Disorders Drug... Dec 2013We review the genetic and clinical features of spinobulbar muscular atrophy (SBMA), a progressive neuromuscular disorder caused by a CAG/glutamine tract expansion in the... (Review)
Review
We review the genetic and clinical features of spinobulbar muscular atrophy (SBMA), a progressive neuromuscular disorder caused by a CAG/glutamine tract expansion in the androgen receptor. SBMA was the first polyglutamine disease to be discovered, and we compare and contrast it with related degenerative disorders of the nervous system caused by expanded glutamine tracts. We review the cellular and animals models that have been most widely used to study this disorder, and highlight insights into disease pathogenesis derived from this work. These model systems have revealed critical aspects of the disease, including its hormone dependence, a feature that underlies disease occurrence only in men with the mutant allele. We discuss how this and other findings have been translated to clinical trials for SBMA patients, and examine emerging therapeutic targets that have been identified by recent work.
Topics: Animals; Clinical Trials as Topic; Drug Delivery Systems; Genetic Therapy; Humans; Molecular Chaperones; Muscular Disorders, Atrophic; Signal Transduction
PubMed: 24040817
DOI: No ID Found -
Bone Nov 2020Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare genetic disorder of extraskeletal bone formation, but could appropriately be viewed as a seminal disorder of... (Review)
Review
Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare genetic disorder of extraskeletal bone formation, but could appropriately be viewed as a seminal disorder of osteochondrogenesis. Many, if not most, of the musculoskeletal features of FOP are related to dysregulated chondrogenesis including abnormal articular cartilage formation, abnormal diarthrodial joint specification, growth plate dysplasia, osteochondroma formation, heterotopic endochondral ossification (HEO), and precocious arthropathy. In FOP, causative activating mutations of Activin receptor A type I (ACVR1), a bone morphogenetic protein (BMP) type I receptor, are responsible for the osteochondrodysplasia that impacts developmental phenotypes as well as postnatal features of this illustrative disorder. Here, we highlight the myriad developmental and postnatal effects on osteochondrogenesis that emanate directly from mutant ACVR1 and dysregulated bone morphogenetic protein (BMP) signaling in FOP.
Topics: Activin Receptors, Type I; Bone Morphogenetic Proteins; Chondrogenesis; Humans; Myositis Ossificans; Ossification, Heterotopic
PubMed: 32730934
DOI: 10.1016/j.bone.2020.115539 -
Current Opinion in Genetics &... Jun 2014A common concept in aging research is that chronological age is the most important risk factor for the development of diverse diseases, including degenerative diseases... (Review)
Review
A common concept in aging research is that chronological age is the most important risk factor for the development of diverse diseases, including degenerative diseases and cancers. The mechanistic link between the aging process and disease pathogenesis, however, is still enigmatic. Nevertheless, measurement of lifespan, as a surrogate for biological aging, remains among the most frequently used assays in aging research. In this review, we examine the connection between 'normal aging' and age-related disease from the point of view that they form a continuum of aging phenotypes. This notion of common mechanisms gives rise to the converse postulate that diseases may be risk factors for accelerated aging. We explore the advantages and caveats associated with using lifespan as a metric to understand cell and tissue aging, focusing on the elucidation of molecular mechanisms and potential therapies for age-related diseases.
Topics: Aging; Animals; Disease; Gene-Environment Interaction; Humans; Longevity; Models, Biological; Mutation; Phenotype; Signal Transduction
PubMed: 25005743
DOI: 10.1016/j.gde.2014.05.004