Edellistä sukupolvea (1920 aikaan)
Aktivaatiossa vaikuttaa NAD/NADH, sekä usea SUMF tekijä, jossa ryhmä SUMF1 ja SUMF2 lisäksi vuorovaikuttavat säädellen ARS mahdollista aktivaatiota. Jos SUMF2 ja SUMF1 ryhmät liittyvät toisiinsa estyy ARS aktaativaatio jolloin nähdään: NADH +(H2S) ja aktiivi ARS.
https://reactome.org/PathwayBrowser/#/R-HSA-163841&SEL=R-HSA-1614336&PATH=R-HSA-392499,R-HSA-597592
(Omaa tekstiäni 11.5. 2023: Arylsulfataasien (ARS) osalta löytää lisätietoja reaktomilinkistä, joka on erikseen seuraavassa otsikossa. Tiesin arylsulfataaseista aikanaan sen, että niissä on K1-vitamiinista riippuvia rakenteita joukossa. Nyt kun etsin GeneCard tietoja arylsulfataaseista ARS huomaan, että muutama niistä inhiboituu warfariinilla, ainakin yksi niistä: ARSE. Olen vielä etsimässä sitä PTM modifikaatiota. Niitä etsiessä löysin reaktomitaulukon, josta ARS-entsyymien aktivaatio kuvataan kaavamaisesti erittelemättä eri ARS tyyppejä tässä yleiskuvassa. Mainitaan jopa erään sars-Cov-2 proteiininkin päässeen SUMF2-ryppään vaikuttajajoukkoon, nim Orf3A. Sars-Cov-2 teki hyvin erikoisen alkutempun. Se sujuttautui jollain tavalla lysosomien suuntaan ja autofagosomiin päin johtavalle tielle, mutta tie jähmettyi eikä johtanut virusta lysosomaaliseen hajoitukseen, vaan itse asiassa virus sai turvallisen kaksoiskalvoiseen sytoplasmiseen linnoituksen, jossa se pääsi toteutumaan kalvorakennelmien suojaamana).
Näitä ARS on paljon ja aakkosia riittää. en ole vielä koonnut koko luetteloa.
https://www.malacards.org/card/parkinson_disease_1_autosomal_dominant
Summaries:
MedlinePlus: 41 Parkinson's disease (PD) is a type of movement disorder. It happens when nerve cells in the brain don't produce enough of a brain chemical called dopamine. Sometimes it is genetic, but most cases do not seem to run in families. Exposure to chemicals in the environment might play a role. Symptoms begin gradually, often on one side of the body. Later they affect both sides. They include: Trembling of hands, arms, legs, jaw and face Stiffness of the arms, legs and trunk Slowness of movement Poor balance and coordination As symptoms get worse, people with the disease may have trouble walking, talking, or doing simple tasks. They may also have problems such as depression, sleep problems, or trouble chewing, swallowing, or speaking. There is no specific test for PD, so it can be difficult to diagnose. Doctors use a medical history and a neurological examination to diagnose it. PD usually begins around age 60, but it can start earlier. It is more common in men than in women. There is no cure for PD. A variety of medicines sometimes help symptoms dramatically. Surgery and deep brain stimulation (DBS) can help severe cases. With DBS, electrodes are surgically implanted in the brain. They send electrical pulses to stimulate the parts of the brain that control movement. NIH: National Institute of Neurological Disorders and Stroke
MalaCards based summary: Parkinson Disease, Late-Onset, also known as parkinson disease, is related to hereditary late-onset parkinson disease and parkinson disease 3, autosomal dominant, and has symptoms including tremor, constipation and myoclonus. An important gene associated with Parkinson Disease, Late-Onset is MAPT (Microtubule Associated Protein Tau), and among its related pathways/superpathways are Parkinson's disease pathway and Degradation pathway of sphingolipids, including diseases. The drugs Idebenone and Tadalafil have been mentioned in the context of this disorder. Affiliated tissues include Brain and subthalamic nucleus, and related phenotypes are hallucinations and abnormal autonomic nervous system physiology
MedlinePlus Genetics: 42 Parkinson disease is a progressive disorder of the nervous system. The disorder affects several regions of the brain, especially an area called the substantia nigra that controls balance and movement.Often the first symptom of Parkinson disease is trembling or shaking (tremor) of a limb, especially when the body is at rest. Typically, the tremor begins on one side of the body, usually in one hand. Tremors can also affect the arms, legs, feet, and face. Other characteristic symptoms of Parkinson disease include rigidity or stiffness of the limbs and torso, slow movement (bradykinesia) or an inability to move (akinesia), and impaired balance and coordination (postural instability). These symptoms worsen slowly over time.Parkinson disease can also affect emotions and thinking ability (cognition). Some affected individuals develop psychiatric conditions such as depression and visual hallucinations. People with Parkinson disease also have an increased risk of developing dementia, which is a decline in intellectual functions including judgment and memory.Generally, Parkinson disease that begins after age 50 is called late-onset disease. The condition is described as early-onset disease if signs and symptoms begin before age 50. Early-onset cases that begin before age 20 are sometimes referred to as juvenile-onset Parkinson disease.
UniProtKB/Swiss-Prot: 73 A complex neurodegenerative disorder characterized by bradykinesia, resting tremor, muscular rigidity and postural instability. Additional features are characteristic postural abnormalities, dysautonomia, dystonic cramps, and dementia. The pathology of Parkinson disease involves the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (intraneuronal accumulations of aggregated proteins), in surviving neurons in various areas of the brain. The disease is progressive and usually manifests after the age of 50 years, although early-onset cases (before 50 years) are known. The majority of the cases are sporadic suggesting a multifactorial etiology based on environmental and genetic factors. However, some patients present with a positive family history for the disease. Familial forms of the disease usually begin at earlier ages and are associated with atypical clinical features.
PubMed Health : 63 Parkinson's: Parkinson's is a disease of the nervous system that mostly affects older people. It typically begins after the age of 50. The disease can be very hard to live with because it severely restricts mobility and as a result makes daily activities increasingly difficult. Parkinson's is a progressive disease, which means that in most cases it will continue to gradually get worse. Many people who develop Parkinson’s will require nursing care. There is no cure for the disease and its exact cause is not known, but there are effective treatments that can relieve the symptoms.
NINDS: 52 Parkinson's disease (PD) is movement disorder of the nervous system that gets worse over time. As nerve cells (neurons) in parts of the brain weaken, are damaged, or die, people may begin to notice problems with movement, tremor, stiffness in the limbs or the trunk of the body, or impaired balance. As symptoms progress, people may have difficulty walking, talking, or completing other simple tasks. Not everyone with one or more of these symptoms has PD, as the symptoms appear in other diseases as well.
OMIM®: 57 Parkinson disease was first described by James Parkinson in 1817. It is the second most common neurodegenerative disorder after Alzheimer disease (AD; 104300), affecting approximately 1% of the population over age 50 (Polymeropoulos et al., 1996). (168600) (Updated 26-Feb-2023)
Disease Ontology 11 Late onset parkinson's disease: A Parkinson's disease characterized by onset of motor symptoms typically after 60 years of age.
Parkinson's disease: A synucleinopathy that has material basis in degeneration of the central nervous system that often impairs motor skills, speech, and other functions.
Wikipedia: 75 Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central... more...
Department of Pediatrics, The University of Texas Southwestern Medical School, Dallas, Texas 75390, USA. Abstract
While unesterified cholesterol (C) is essential for remodeling neuronal plasma membranes, its role in certain neurodegenerative disorders remains poorly defined. Uptake of sterol from pericellular fluid requires processing that involves two lysosomal proteins, lysosomal acid lipase, which hydrolyzes C esters, and NPC1 (Niemann-Pick type C1). In systemic tissues, inactivation of either protein led to sterol accumulation and cell death, but in the brain, inactivation of only NPC1 caused C sequestration and neurodegeneration. When injected into the CNS of the npc1(-/-) mouse, 2-hydroxypropyl-β-cyclodextrin (HP-β-CD), a compound known to prevent this C accumulation, diffused throughout the brain and was excreted with a t(½) of 6.5 h. This agent caused suppression of C synthesis, elevation of C esters, suppression of sterol regulatory-binding protein 2 (SREBP2) target genes, and activation of liver X receptor-controlled genes. These findings indicated that HP-β-CD promoted movement of the sequestered C from lysosomes to the metabolically active pool of C in the cytosolic compartment of cells in the CNS. The ED(50) for this agent in the brain was ∼0.5 mg/kg, and the therapeutic effect lasted >7 d. Continuous infusion of HP-β-CD into the ventricular system of npc1(-/-) animals between 3 and 7 weeks of age normalized the biochemical abnormalities and completely prevented the expected neurodegeneration. These studies support the concept that neurons continuously acquire C from interstitial fluid to permit plasma membrane turnover and remodeling. Inactivation of NPC1 leads to lysosomal C sequestration and neurodegeneration, but this is prevented by the continuous, direct administration of HP-β-CD into the CNS.
