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Neurodegenerative
A neurodegenerative disease is caused by the progressive loss of neurons, in the process known as neurodegeneration. Neuronal damage may also ultimately result in their death. Neurodegenerative diseases include amyotrophic lateral sclerosis, multiple sclerosis, Parkinson's disease, Alzheimer's disease, Huntington's disease, multiple system atrophy, tauopathies, and prion diseases. Neurodegeneration can be found in the brain at many different levels of neuronal circuitry, ranging from molecular to systemic. Because there is no known way to reverse the progressive degeneration of neurons, these diseases are considered to be incurable; however research has shown that the two major contributing factors to neurodegeneration are oxidative stress and inflammation. Biomedical research has revealed many similarities between these diseases at the subcellular level, including atypical protein assemblies (like proteinopathy) and induced cell death. These similarities suggest that therapeut ...
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Alzheimers Brain
Alzheimer's disease (AD) is a neurodegenerative disease and the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in remembering recent events. As the disease advances, symptoms can include problems with language, disorientation (including easily getting lost), mood swings, loss of motivation, self-neglect, and behavioral issues. As a person's condition declines, they often withdraw from family and society. Gradually, bodily functions are lost, ultimately leading to death. Although the speed of progression can vary, the average life expectancy following diagnosis is three to twelve years. The causes of Alzheimer's disease remain poorly understood. There are many environmental and genetic risk factors associated with its development. The strongest genetic risk factor is from an allele of apolipoprotein E. Other risk factors include a history of head injury, clinical depression, and high blood pressure. The progression of the disease ...
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Alzheimer's Disease
Alzheimer's disease (AD) is a neurodegenerative disease and the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in remembering recent events. As the disease advances, symptoms can include problems with language, disorientation (including easily getting lost), mood swings, loss of motivation, self-neglect, and behavioral issues. As a person's condition declines, they often withdraw from family and society. Gradually, bodily functions are lost, ultimately leading to death. Although the speed of progression can vary, the average life expectancy following diagnosis is three to twelve years. The causes of Alzheimer's disease remain poorly understood. There are many environmental and genetic risk factors associated with its development. The strongest genetic risk factor is from an allele of apolipoprotein E. Other risk factors include a history of head injury, clinical depression, and high blood pressure. The progression of the di ...
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Dementia
Dementia is a syndrome associated with many neurodegenerative diseases, characterized by a general decline in cognitive abilities that affects a person's ability to perform activities of daily living, everyday activities. This typically involves problems with memory, thinking, behavior, and motor control. Aside from memory impairment and a thought disorder, disruption in thought patterns, the most common symptoms of dementia include emotional problems, difficulties with language, and decreased motivation. The symptoms may be described as occurring in a continuum (measurement), continuum over several stages. Dementia is a life-limiting condition, having a significant effect on the individual, their caregivers, and their social relationships in general. A diagnosis of dementia requires the observation of a change from a person's usual mental functioning and a greater cognitive decline than might be caused by the normal aging process. Several diseases and injuries to the brain, ...
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Parkinson's Disease
Parkinson's disease (PD), or simply Parkinson's, is a neurodegenerative disease primarily of the central nervous system, affecting both motor system, motor and non-motor systems. Symptoms typically develop gradually and non-motor issues become more prevalent as the disease progresses. The motor symptoms are collectively called parkinsonism and include tremors, bradykinesia, spasticity, rigidity as well as postural instability (i.e., difficulty maintaining balance). Non-motor symptoms develop later in the disease and include behavior change (individual), behavioral changes or mental disorder, neuropsychiatric problems such as sleep abnormalities, psychosis, anosmia, and mood swings. Most Parkinson's disease cases are idiopathic disease, idiopathic, though contributing factors have been identified. Pathophysiology involves progressive nerve cell death, degeneration of nerve cells in the substantia nigra, a midbrain region that provides dopamine to the basal ganglia, a system invo ...
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Proteinopathy
In medicine, proteinopathy ( 'pref''. protein -pathy 'suff''. disease proteinopathies ''pl''.; proteinopathic ''adj''), or proteopathy, protein conformational disorder, or protein misfolding disease, is a class of diseases in which certain proteins become structurally abnormal, and thereby disrupt the function of cells, tissues and organs of the body. Often the proteins fail to fold into their normal configuration; in this misfolded state, the proteins can become toxic in some way (a toxic gain-of-function) or they can lose their normal function. The proteinopathies include such diseases as Creutzfeldt–Jakob disease (and a variant associated with mad cow disease) and other prion diseases, Alzheimer's disease, Parkinson's disease, amyloidosis, multiple system atrophy, and a wide range of other disorders. The term ''proteopathy'' was first proposed in 2000 by Lary Walker and Harry LeVine. The concept of proteopathy can trace its origins to the mid-19th century, wh ...
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Huntington's Disease
Huntington's disease (HD), also known as Huntington's chorea, is an incurable neurodegenerative disease that is mostly Genetic disorder#Autosomal dominant, inherited. It typically presents as a triad of progressive psychiatric, cognitive, and motor symptoms. The earliest symptoms are often subtle problems with mood or mental/psychiatric abilities, which precede the motor symptoms for many people. The definitive physical symptoms, including a general Ataxia, lack of coordination and an unsteady human gait, gait, eventually follow. Over time, the basal ganglia region of the brain gradually Basal ganglia disease#Huntington's disease, becomes damaged. The disease is primarily characterized by a distinctive hyperkinesia, hyperkinetic movement disorder known as ''chorea.'' Chorea classically presents as uncoordinated, involuntary, "dance-like" body movements that become more apparent as the disease advances. Physical abilities gradually worsen until Motor coordination, coordinated mo ...
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Amyotrophic Lateral Sclerosis
Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND) or—in the United States—Lou Gehrig's disease (LGD), is a rare, Terminal illness, terminal neurodegenerative disease, neurodegenerative disorder that results in the progressive loss of both upper and lower motor neurons that normally control Skeletal muscle, voluntary muscle contraction. ALS is the most common form of the motor neuron diseases. ALS often presents in its early stages with gradual muscle Spasticity, stiffness, Fasciculation, twitches, Muscle weakness, weakness, and Muscle atrophy, wasting. Motor neuron loss typically continues until the abilities to eat, speak, move, and, lastly, breathe are all lost. While only 15% of people with ALS also fully develop frontotemporal dementia, an estimated 50% face at least some minor difficulties with cognitive disorder, thinking and behavior. Depending on which of the aforementioned symptoms develops first, ALS is classified as ''limb-onset'' (b ...
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Multiple System Atrophy
Multiple system atrophy (MSA) is a rare neurodegenerative disorder characterized by tremors, slow movement, muscle rigidity, postural instability (collectively known as parkinsonism), autonomic dysfunction and ataxia. This is caused by progressive degeneration of neurons in several parts of the brain including the basal ganglia, inferior olivary nucleus, and cerebellum. MSA was first described in 1960 by Milton Shy and Glen Drager and was then known as Shy–Drager syndrome. Many people affected by MSA experience dysfunction of the autonomic nervous system, which commonly manifests as orthostatic hypotension, impotence, loss of sweating, dry mouth and urinary retention and incontinence. Palsy of the vocal cords is an important and sometimes initial clinical manifestation of the disorder. A prion of the alpha-synuclein protein within affected neurons may cause MSA. About 55% of MSA cases occur in men, with those affected first showing symptoms at the age of 50–60 ye ...
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Oxidative Stress
Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage. Disturbances in the normal redox state of cells can cause toxic effects through the production of peroxides and free radicals that damage all components of the cell, including proteins, lipids, and DNA. Oxidative stress from oxidative metabolism causes base damage, as well as strand breaks in DNA. Base damage is mostly indirect and caused by the reactive oxygen species generated, e.g., (superoxide radical), OH ( hydroxyl radical) and (hydrogen peroxide). Further, some reactive oxidative species act as cellular messengers in redox signaling. Thus, oxidative stress can cause disruptions in normal mechanisms of cellular signaling. In humans, oxidative stress is thought to be involved in the development of attention deficit hyperactivity disorder, cancer, Parkin ...
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Synapse
In the nervous system, a synapse is a structure that allows a neuron (or nerve cell) to pass an electrical or chemical signal to another neuron or a target effector cell. Synapses can be classified as either chemical or electrical, depending on the mechanism of signal transmission between neurons. In the case of electrical synapses, neurons are coupled bidirectionally with each other through gap junctions and have a connected cytoplasmic milieu. These types of synapses are known to produce synchronous network activity in the brain, but can also result in complicated, chaotic network level dynamics. Therefore, signal directionality cannot always be defined across electrical synapses. Chemical synapses, on the other hand, communicate through neurotransmitters released from the presynaptic neuron into the synaptic cleft. Upon release, these neurotransmitters bind to specific receptors on the postsynaptic membrane, inducing an electrical or chemical response in the target neuron ...
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Neurofibrillary Tangle
Neurofibrillary tangles (NFTs) are intracellular aggregates of hyperphosphorylated tau protein that are most commonly known as a primary Biomarker (medicine), biomarker of Alzheimer's disease. Their presence is also found in numerous other diseases known as Tauopathy, tauopathies. Little is known about their exact relationship to the different pathologies. Formation Neurofibrillary tangles are formed by phosphorylation, hyperphosphorylation of a microtubule-associated protein known as tau (protein), tau, causing it to aggregate, or group, in an insoluble form. (These aggregations of hyperphosphorylated tau protein are also referred to as PHF, or "paired helical filaments"). The precise mechanism of tangle formation is not completely understood, though it is typically recognized that tangles are a primary causative factor in neurodegenerative disease. Cytoskeletal changes Three different maturation states of NFT have been defined using anti-tau and anti-ubiquitin immunostaining. ...
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Tauopathy
Tauopathies are a class of neurodegenerative diseases characterized by the aggregation of abnormal tau protein. Hyperphosphorylation of tau proteins causes them to dissociate from microtubules and form insoluble aggregates called neurofibrillary tangles. Various neuropathologic phenotypes have been described based on the anatomical regions and cell types involved as well as the unique tau isoforms making up these deposits. The designation 'primary tauopathy' is assigned to disorders where the predominant feature is the deposition of tau protein. Alternatively, diseases exhibiting tau pathologies attributed to different and varied underlying causes are termed 'secondary tauopathies'. Some neuropathologic phenotypes involving tau protein are Alzheimer's disease, frontotemporal dementia, progressive supranuclear palsy, and corticobasal degeneration. Tau protein Tau protein, also called tubulin associated unit or microtubule-associated protein tau (MAPT), is a microtubule-associate ...
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