Parkinson's disease

 

 

Genes that have been associated with Parkinson's disease RSS feeds link to Pubmed

GWAS from Genome.gov

AAK1 ACMSD ATF6 BMP4 BRDG1 BST1 C10orf32 C17orf69 ISM1 (c20orf82) CCDC62 CNNM2 CYP17A1 DBC1 DGKQ DLG2 DSG3 EIF4G1 GAK GBA HIP1R HLA-DRB5 IMP5 ITGA8 KIAA1267 LAMP3 LOC644246 MAPT MCCC1 MMRN1 NSF NUCKS1 OCA2 PARK16 PLEKHM1 PM20D1 PRRG4 QSER1 RAB7L1 RAI1 RIT2 SCARB2 SEMA5A SLC41A1 SNCA SREBF1 STBD1 STK39 SYT11 SYT4 TAS1R2 UNC13B USP25 WNT3

Pre GWAS and others: Data from various sources including Pubmed alerts A B and : PDGene developed by the Max Planck Institute for molecular genetics, Berlin; The Michael J Fox foundation , and the Alzheimer Research forum See also The Genetic Association database at NIH ... Genotator at Harvard University and HUGE navigator See also PDBase The Parkinson Disease Mutation Database Leiden Open Variation Database ..Mutation database for Parkinson's disease

Copy number variations

Parkinson's epistasis

MicroRNA's implicated in Parkinson's disease

Need KEGG mapping: CHRNA5 DNAJC6 SIRT1 LAMP2 HLA-DRB1 . ATG7 . HER2 SMPD1 ATP6AP2 (mutation) FBXO7 S100B. NOD2 HLA-DQA1 AGER . SHMT CHRNB3 LAMP3 ESR1 S1PR1 OLFM3 LRPAP1 PGLYRP2 PGLYRP3 PGLYRP4 NCAPD2 STX1B TLR9 TLR2 TLR4 CHCHD2 MC1R ALDH2 . CHRNA4 TMEM230

Viral and other infections Wikipedia and Reference
  • Encephalitis Lethargica possibly related to the 1918 flu pandemic Treatment of these patients with L-DOPA, recorded in the film Awakenings helped to revolutionise Parkinson's disease therapy Foley 2009
    • An enterovirus , as well as the poliovirus and coxsackievirus B have been linked to this condition (electron-microscope study of archived post-mortem tissue) Dourmashkin et al, 2012 and 2018
  • Influenza infection has been related to Substantia nigra cell loss in Man Mihara et al, 2001
  • Influenza H1N1 infection in mice targets the Substantia nigra and kills dopamine neurones Jang et al, 2009
    • The influenza virus has been recorded in the substantia nigra of Parkinson's disease brains Rohn and Catlin, 2011
  • The Epstein-Barr virus can cause post-encephalitic Parkinsonism Espay and Henderson, 2011
  • CSF antibodies to coronavirus have been observed in some patients Fazzini et al, 1992
  • Post-mortem brain viral DNA
    • HSV-1: Control 25%: PD 17.5% .
    • HHV-6: Control 87.5% PD 75%
    • Varicella: Control 27.5% PD 40% Hemling et al, 2003
  • Hepatitis C infection associated with Parkinson's disease: Viral infection caused dopaminergic neuronal death in the midbrain neuron-glia coculture system in rats Wu et al, 2015 Tsai et al, 2015
  • Hepatitis B and Hepatitis C infection associated with Parkinson's disease Pakpoor et al, 2017
  • Hepatitis C infection associated with Parkinson's disease risk (meta-analysis) Wijarnpreecha et al, 2018
  • Serum and CSF antibodies: Herpes simplex virus 1 , measles, and rubella antibody titres were lower in sera of PD patients: Serum influenza antibody titres were higher in post-encephalitic Parkinsonism Elizan et al, 1979
  • Association with Japanese B encephalitis virus Das et al, 2011
  • The incidence of Parkinson's disease, as well as that of many other disorders has been reported to be increased in poliomyelitis survivors Kang and Lin, 2011
  • Mumps, influenza , whooping cough and herpes simplex infections have been associated with Parkinson;s disease (adjusted by occupation and family history )Vlajinac et al, 2012 In a further study Parkinson's disease was significantly related to mumps [odds ratio adjusted on occupation and family history of PD (aOR) = 7.86, 95% confidence interval (CI) = 3.77-16.36], scarlet fever (aOR = 12.18, 95% CI = 1.97-75.19), influenza (aOR = 8.01, 95% CI = 4.61-13.92), whooping cough (aOR = 19.90, 95% CI = 2.07-190.66) and herpes simplex infections (aOR = 11.52, 95% CI = 2.25-58.89). Tuberculosis, measles and chicken pox were not associated with PD Vlajinac et al, 2013
  • Childhood measles has been inversely associated with Parkinson's disease Harris et al, 2012
  • The Borna virus has been implicated in Parkinson's disease Zhang et al, 2013
  • No association with Arbovirus antibodies Elizan et al, 1978
  • A possible association with Toxoplasma Gondii has been reported in Turkey Miman et al, 2010
  • Transient Parkinsonism has been observed in West Nile virus encephalitis Robinson et al, 2003 Dopaminergic drugs inhibit West Nile virus replication in cell culture Blazquez et al, 2016
  • An increased incidence of Parkinson's disease has been observed following a whooping cough epidemic (Bordetella pertussis) de Pedro-Cuesta et al, 1996
  • Nocardia asteroides infects many old people and has been implicated in Parkinson's disease Kohbata et al, 1993. Infection with this bacterium in mice kills Substantia nigra neurones Tam et al, 2002
  • formyl-methionyl-leucyl-phenylalanine , also a bacterial product kills dopamine neurones Gao et al, 2008
  • Helicobacter pylori seropositivity has been associated with Parkinson's disease Charlett et al, 1999
  • Helicobacter Suis observed at greater frequency in Parkinson's disease patients Blaecher et al, 2013
  • Increased dental loss associated with increased cariogenic bacteria Einarsdóttir et al, 2009
    • Abnormal oral colonisation by gram-negative bacteria (Escherichia coli , Klebsiella, Kluyvera , Serratia , Proteus and Enterobacter species) Gosney et al, 2003
  • Increased Staphylococcus aureus in conjunctival flora Kusbeci et al, 2009
  • A case of Parkinson's disease secondary to neurosyphilis Spitz et al, 2008
  • Reduced risk associated with childhood viral infection particularly measles Sasco et al, 1985
  • Increased antibody response to Herpes simplex in Parkinson's disease patients Martilla and Rinne, 1981
  • Case report of Parkinsonism produced by gram-negative sepsis Alasia et al, 2006
  • Case report of Parkinsonism associated with cryptococcal abscesses of the basal ganglia Camargos et al, 2006
  • Parkinsonism asociated with streptococcal infection McKee and Sussman, 2005
  • A mild form of acute Parkinson's disease has been observed after a wasp sting Leopold et al, 1999
  • Chronic polysystemic candidiasis produces acetaldehyde, which upon reaction with dopamine can produce the neurotoxin Salsalinol Epp and Mravec 2006
  • Infectious burden consisting of cytomegalovirus , Epstein-Barr virus , herpes simplex (HSV-1), B. burgdorferi, C. pneumoniae and H. pylori is associated with PD Bu et al, 2015
  • Alpha-synuclein restricts brain viral infection (West Nile virus and Venezuelan equine encephalitis virus) in mice Beatman et al, 2015. alpha-synuclein also has antimicrobial properties against bacteria (Escherichia coli and Staphylococcus aureus)and fungi ( Aspergillus flavus, Aspergillus fumigatus and Rhizoctonia solani) Park et al, 2016
Chemicals implicated in Parkinson's disease
  • MPTP causes Parkinsonism Langston et al, 1983
  • Paraquat and rotenone have been implicated as environmental toxins MPTP, Rotenone and paraquat all block the mitochondrial respiratory chain, although there are differences in precise mechanismsArif and Khan, 2010
    • The effects of paraquat on dopaminergic neurones in mice are attenuated by intergeron gamma ( IFNG ) knockout Mangano et al, 2011 , as are those of MPTP : IFNG also kills dopamine neurones, but only in the presence of microglia Mount et al 2007
    • Vitamin K2 has been reported to reverse mitochondrial deficits in PINK1 deficient Drosophila Vos et al, 2012
  • Lipopolysaccharide intracerebral injection causes Parkinsonism like effects and dopaminergic damage in rodents Castaño et al, 1998 (LPS is a component of many bacteria)
  • Ammonium chloride and tunicamycin kill dopamine neurones (in fish) Matsui et al, 2010
  • Exposure to pesticides has been associated with Parkinson's disease Hatcher et al, 2008
  • PD incidence associated with exposure to certain pesticide ingredients such as alachlor and broxomy in Nebraska Wan and Lin, 2016
  • Milk intake is associated with substantia nigra neuronal loss in post-mortem brains unaffected by Parkinson's disease. Residues of heptachlor epoxide found in 9 of 10 brains in those with high milk consumption Abbott et al, 2016
  • Household orgabophospate pesticide use associated with an increased risk of Parkinson's disease Narayan et al, 2013
  • For every 1.0 µg/L of pesticide in groundwater, the risk of PD increases by 3% (well water samples with atrazine, simazine, alachlor, and metolachlor measurements) James and Hall, 2015
  • B4GALNT1 (beta-1,4-N-acetyl-galactosaminyl transferase 1 ) knockdown produces parkinsonism in mice (synthesises ganglosides) Kegg pathway .Wu et al, 2011
  • Elevated serum levels of the organochlorine pesticide ß-hexachlorocyclohexane have been reported in Parkinsonian patients Richardson et al, 2011
  • Trichloroethylene inhibits mitochondrial respiration and has been implicated in Parkinson's disease Gash et al, 2008: perchloroethylene and carbon tetrachloride tended toward significance as risk factors Goldman et al, 2012
  • Polychlorinated biphenyls have been linked to Parkinson's disease pathology, particularly in females Hatcher-Martin et al, 2012.
  • Pesticides and Parkinson's disease database
  • TEMPEST : A Task Exposure Matrix for Pesticides : Various studies
  • The consumption of whalemeat and blubber (probably a concentration of food chain toxins) has been linked to Parkinson's disease: beta-hexachlorocyclohexane was also linked to increased risk Petersen et al, 2008
  • BMAA ( beta-Methylamino-L-alanine ), a toxin derived from Cycad seeds causes a degenerative disease with Parkinsonian features in Guam Vyas and Weiss, 2009 . BMAA can also be produced by cyanobacteria Cox et al, 2003
  • Methamphetamine use has been implicated as a risk factor Callaghan et al, 2010
  • A metabolite from S. venezuelae kills dopaminergic neurones in nematodes and in mammalian SH-SY5Y cells Caldwell et al, 2009
  • Organophosphate pesticides have been linked to Parkinson's disease Das et al, 2011 Wang et al, 2014
  • Fungal-derived 1-octen-3-ol (mushroom alcohol) causes dopaminergic neurodegeneration in Drosophila Inamdar et al, 2013
  • 2-Amino-1-Methyl-6-Phenylimidazo[4,5-b]Pyridine, a byproduct of cooked meat, is toxic to dopaminergic neurones Griggs et al, 2014
  • Exposure to extremely low frequency magnetic fields associated with PD Brouwer et al, 2015

Metals and Parkinson's disease

  • Previous exposure to manganese has been associated with increased risk Park et al, 2005
  • Urban Parkinson disease incidence is higher in US counties with high industrial release of copper or manganese Willis et al, 2010
  • A significant correlation between blood manganese and signal intensity in T1-weighted MRI images has been reported in liver-disease patients with Parkinson-like signs Hudnell, 1999
  • Cumulative lead exposure has been associated with Parkinson's disease Weisskopf et al, 2010
  • Significantly lower levels of Cobalt, Chromium, Iron, Lead, Silicon and Tin were observed in the CSF of PD patients compared with those in controls, with a percentage depletion of up to 50% for Chromium and Lead Alimonti et al, 2007.
  • Decreased Aluminium , Sulphur, Iron and zinc plasma concentrations: Increased potassium, Magnesium and Copper concentrations Hegde et al, 2004
  • Increased serum iron levels causally associated with a decreased risk of developing PD Pichler et al, 2013.
  • Aluminium, copper, iron, manganese and zinc abnormalities contribute to risk Ahmed and Santosh 2010
  • Occupational exposure to mercury increases the risk of hospital admissions for neurological, Parkinson's or renal diseases Thygesen et al, 2011

 

Environmental and dietary
  • Early exposure to a rural environment associated with increased risk (see pesticides)Rajput et al, 1987
  • Working in agriculture, hunting, and forestry has been associated with increased risk Park et al, 2005
  • Parkinson's disease patients tend to have had fewer domestic animals at home during their lifetime, including cows, sheep, pigs, and chickens Kuopio et al, 1999.
  • Dietary vegetables, lutein, xanthophylls, xanthins, carbohydrates, monosaccharides, junk food, refined sugar, lactose, animal fat, total fat, nuts and seeds, tea, Iron, and total energy associated with increased risk: Ishihara and Brayne, 2005
  • Disease incidence inversely associated with N-3 polyunsaturated fatty acids and the N-3 precursor alpha-linolenic acid and dietary fats modified the association of PD risk with pesticide exposure Kamel et al, 2014.
  • Dietary fish, egg, potatoes, bread, alcohol, coffee, tea, niacin, pantothenic acid, folate and pyridoxine associated with reduced risk Ishihara and Braine,2005 See also Skeie et al, 2010
    • The coffee-PD association was strongest among slow metabolizers of caffeine who were homozygous carriers of CYP1A2 polymorphisms Popat et al, 2011.
  • Dietary patterns with a high intake of fruit, vegetables, legumes, whole grains, nuts, fish, and poultry and a low intake of saturated fat and a moderate intake of alcohol may protect against Parkinson's disease.Gao et al,1997
  • Milk intake in midlife has been associoated with a higher risk of developing Parkinson's disease Park et al, 2005
  • Higher dietary intake of vitamin B6 was associated with a significantly decreased risk of Parkinson's disease, in smokers De Lau et al, 2006
  • Living near rubber plants and drinking river water asociated with increased risk in China Wang et al, 1993
  • An inverse association with cigarette smoking has been observedHernan et al, 2001
  • Tobacco chewing protected and hypertension increased Parkinson's disease incidence in an Indian study Das et al, 2010.
  • Moderate caffeine intake may have a protective effect Ascherio et al, 2001
  • Hormone replacement therapy has little effect but may modify the effects of caffeine and smoking Simon et al, 2009
  • Black tea consumption inversely associated with Parkinson's disease in China Tan et al, 2008
  • Non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDS) may have a beneficial effect Ghang and Power, 2010 Aspirin and salicylate also block the neurotoxic effects of MPTP Aubin et al, 1998
  • Ibuprofen may reduce the risk of developing Parkinson's disease Gao et al, 2011
  • Inverse association between the intakes of beta-carotene or ascorbic acid and Parkinson's disease Sepcic et al, 1993
  • Flavonoid rich foods (tea, berry fruits, apples, red wine, and orange/orange juice) have been reported to reduce the risk of developing Parkinson's disease Gao et al, 2012
  • Parkinson's disease risk is reduced in men working outdoors (possible relationship with Vitamin D and sunlight) Kenborg et al, 2010
  • Well water drinking as well as exposure to insecticides and pesticides has been associated with Parkinson's disease Das et al, 2011
  • Hypnotic, anxiolytic or antidepressant drug use for more than 1 year has been associated with Parkinson's disease Dick et al, 2007
  • Under-nutrition is a problem for around 15% of community dwelling people with Parkinson's disease Jaafar et al, 2010
  • Oral contraceptive use (over 10 years) has been associated with lower PD risk in women, while short term but not long-term menopausal hormone therapy was associated with increased risk Liu et al, 2013

Biochemistry and biomarkers

Comorbidity and others

Pesticides and Parkinson’s Disease an open access book chapter

 

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The worldwide distribution of Parkinson's disease: from Wikipedia and Lokal_profil

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