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Catecholaldehyde Hypothesis
The catecholaldehyde hypothesis is a scientific theory positing that neurotoxicity, neurotoxic aldehyde metabolites of the catecholamine neurotransmitters dopamine and norepinephrine are responsible for neurodegenerative diseases involving loss of catecholaminergic neurons, for instance Parkinson's disease. The specific metabolites thought to be involved include 3,4-dihydroxyphenylacetaldehyde (DOPAL) and 3,4-dihydroxyphenylglycolaldehyde (DOPEGAL), which are formed from dopamine and norepinephrine by monoamine oxidase, respectively. These metabolites are subsequently inactivated and detoxification, detoxified by aldehyde dehydrogenase (ALDH). DOPAL and DOPEGAL are monoaminergic neurotoxins in preclinical research, preclinical models and enzyme inhibition, inhibition of and gene polymorphism, polymorphisms in ALDH are associated with Parkinson's disease. The catecholaldehyde hypothesis additionally posits that DOPAL oligomerization, oligomerizes with α-synuclein resulting in accum ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Aldehyde Dehydrogenase
Aldehyde dehydrogenases () are a group of enzymes that catalyse the oxidation of aldehydes. They convert aldehydes (R–C(=O)) to carboxylic acids (R–C(=O)). The oxygen comes from a water molecule. To date, nineteen ALDH genes have been identified within the human genome. These genes participate in a wide variety of biological processes including the detoxification of exogenously and endogenously generated aldehydes. Function Aldehyde dehydrogenase is a polymorphic enzyme responsible for the oxidation of aldehydes to carboxylic acids. There are three different classes of these enzymes in mammals: class 1 (low ''K''m, cytosolic), class 2 (low ''K''m, mitochondrial), and class 3 (high ''K''m, such as those expressed in tumors, stomach, and cornea). In all three classes, constitutive and inducible forms exist. ALDH1 and ALDH2 are the most important enzymes for aldehyde oxidation, and both are tetrameric enzymes composed of 54 kDa subunits. These enzymes are ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Dopamine
Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. It is an amine synthesized by removing a carboxyl group from a molecule of its precursor chemical, L-DOPA, which is synthesized in the brain and kidneys. Dopamine is also synthesized in plants and most animals. In the brain, dopamine functions as a neurotransmitter—a chemical released by neurons (nerve cells) to send signals to other nerve cells. The brain includes several distinct dopamine pathways, one of which plays a major role in the motivational component of reward-motivated behavior. The anticipation of most types of rewards increases the level of dopamine in the brain, and many addictive drugs increase dopamine release or block its reuptake into neurons following release. Other brain dopamine pathways are involved in motor control and in controllin ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Catecholamines
A catecholamine (; abbreviated CA), most typically a 3,4-dihydroxyphenethylamine, is a monoamine neurotransmitter, an organic compound that has a catechol (benzene with two hydroxyl side groups next to each other) and a side-chain amine. Catechol can be either a free molecule or a substituent of a larger molecule, where it represents a 1,2-dihydroxybenzene group. Catecholamines are derived from the amino acid tyrosine, which is derived from dietary sources as well as synthesis from phenylalanine. Catecholamines are water-soluble and are 50% bound to plasma proteins in circulation. Included among catecholamines are epinephrine (adrenaline), norepinephrine (noradrenaline), and dopamine. Release of the hormones epinephrine and norepinephrine from the adrenal medulla of the adrenal glands is part of the fight-or-flight response. Tyrosine is created from phenylalanine by hydroxylation by the enzyme phenylalanine hydroxylase. Tyrosine is also ingested directly from dietar ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Biological Hypotheses
Biology is the scientific study of life and living organisms. It is a broad natural science that encompasses a wide range of fields and unifying principles that explain the structure, function, growth, origin, evolution, and distribution of life. Central to biology are five fundamental themes: the cell as the basic unit of life, genes and heredity as the basis of inheritance, evolution as the driver of biological diversity, energy transformation for sustaining life processes, and the maintenance of internal stability (homeostasis). Biology examines life across multiple levels of organization, from molecules and cells to organisms, populations, and ecosystems. Subdisciplines include molecular biology, physiology, ecology, evolutionary biology, developmental biology, and systematics, among others. Each of these fields applies a range of methods to investigate biological phenomena, including scientific method, observation, experimentation, and mathematical modeling. Modern bio ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Aging-associated Diseases
An aging-associated disease (commonly termed age-related disease, ARD) is a disease that is most often seen with increasing frequency with increasing senescence. They are essentially complications of senescence, distinguished from the aging process itself because all adult animals age ( with rare exceptions) but not all adult animals experience all age-associated diseases. The term does not refer to age-specific diseases, such as the childhood diseases chicken pox and measles, only diseases of the elderly. They are also not accelerated aging diseases, all of which are genetic disorders. Examples of aging-associated diseases are atherosclerosis and cardiovascular disease, cancer, arthritis, cataracts, osteoporosis, type 2 diabetes, hypertension and Alzheimer's disease. The incidence of all of these diseases increases exponentially with age. Of the roughly 150,000 people who die each day across the globe, about two thirds—100,000 per day—die of age-related causes. In ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Amyloid Hypothesis
The biochemistry of Alzheimer's disease, the most common cause of dementia, is not yet very well understood. Alzheimer's disease (AD) has been identified as a proteopathy: a protein misfolding disease due to the accumulation of abnormally folded amyloid beta (Aβ) protein in the brain. Amyloid beta is a short peptide that is an abnormal proteolytic byproduct of the transmembrane protein amyloid-beta precursor protein (APP), whose function is unclear but thought to be involved in neuronal development. The presenilins are components of proteolytic complex involved in APP processing and degradation. Amyloid beta monomers are soluble and contain short regions of beta sheet and polyproline II helix secondary structures in solution, though they are largely alpha helical in membranes; however, at sufficiently high concentration, they undergo a dramatic conformational change to form a beta sheet-rich tertiary structure that aggregates to form amyloid fibrils. These fibrils and oligomeric ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Cytotoxicity
Cytotoxicity is the quality of being toxic to cells. Examples of toxic agents are toxic metals, toxic chemicals, microbe neurotoxins, radiation particles and even specific neurotransmitters when the system is out of balance. Also some types of drugs, e.g alcohol, and some venom, e.g. from the puff adder (''Bitis arietans'') or brown recluse spider (''Loxosceles reclusa'') are toxic to cells. Cell physiology Treating cells with the cytotoxic compound can result in a variety of prognoses. The cells may undergo necrosis, in which they lose membrane integrity and die rapidly as a result of cell lysis. The cells can stop actively growing and dividing (a decrease in cell viability), or the cells can activate a genetic program of controlled cell death (apoptosis). Cells undergoing necrosis typically exhibit rapid swelling, lose membrane integrity, shut down metabolism, and release their contents into the environment. Cells that undergo rapid necrosis in vitro do not have sufficient ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Synucleinopathy
Synucleinopathies (also called α-Synucleinopathies) are neurodegenerative diseases characterised by the abnormal accumulation of aggregates of alpha-synuclein protein in neurons, nerve fibres or glial cells. There are three main types of synucleinopathy: Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). Other rare disorders, such as various neuroaxonal dystrophies, also have α-synuclein pathologies. Additionally, autopsy studies have shown that around 6% of sporadic Alzheimer's Disease exhibit α-synuclein positive Lewy pathology, and are sub-classed as Alzheimer's Disease with Amygdalar Restricted Lewy Bodies (AD/ALB). Presentation The synucleinopathies have shared features of parkinsonism, impaired cognition, sleep disorders, and visual hallucinations. Synucleinopathies can sometimes overlap with tauopathies, possibly because of interaction between the synuclein and tau proteins. REM sleep behavior disorder (RBD) is a parasomnia ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
α-synuclein
Alpha-synuclein (aSyn) is a protein that in humans is encoded by the ''SNCA'' gene. It is a neuronal protein involved in the regulation of synaptic vesicle trafficking and the release of neurotransmitters. Alpha-synuclein is abundant in the brain, with smaller amounts present in the heart, muscles, and other tissues. Within the brain, it is primarily localized to the axon terminals of presynaptic neurons. There, it interacts with phospholipids and other proteins. Presynaptic terminals release neurotransmitters from specialized compartments called synaptic vesicles, a process essential for neuronal communication and normal brain function. In Parkinson's disease and related synucleinopathies, abnormal, insoluble forms of alpha-synuclein accumulate within neurons as inclusions known as Lewy bodies. Mutations in the ''SNCA'' gene are linked to familial forms of Parkinson's disease. During the process of seeded nucleation, alpha-synuclein adopts a cross-beta sheet structure charac ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Oligomerization
In chemistry and biochemistry, an oligomer () is a molecule that consists of a few repeating units which could be derived, actually or conceptually, from smaller molecules, monomers.Quote: ''Oligomer molecule: A molecule of intermediate relative molecular mass, the structure of which essentially comprises a small plurality of units derived, actually or conceptually, from molecules of lower relative molecular mass.'' The name is composed of Greek elements '' oligo-'', "a few" and '' -mer'', "parts". An adjective form is ''oligomeric''. The oligomer concept is contrasted to that of a polymer, which is usually understood to have a large number of units, possibly thousands or millions. However, there is no sharp distinction between these two concepts. One proposed criterion is whether the molecule's properties vary significantly with the removal of one or a few of the units. An oligomer with a specific number of units is referred to by the Greek prefix denoting that number, wi ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Gene Polymorphism
A gene is said to be polymorphic if more than one allele occupies that gene's Locus (genetics), locus within a population. In addition to having more than one allele at a specific locus, each allele must also occur in the population at a rate of at least 1% to generally be considered polymorphic. Gene polymorphisms can occur in any region of the genome. The majority of polymorphisms are silent, meaning they do not alter the function or expression of a gene. Some polymorphisms are visible. For example, in dogs the E locus can have any of five different alleles, known as E, Em, Eg, Eh, and e. Varying combinations of these alleles contribute to the pigmentation and patterns seen in dog coats. A polymorphic variant of a gene can lead to the abnormal expression or to the production of an abnormal form of the protein; this abnormality may cause or be associated with disease. For example, a polymorphic variant of the gene encoding the enzyme CYP4A11, in which thymidine replaces cytosin ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
