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General Information
Parkinson disease 1
FlyBase ID
Disease Ontology Term
Parent Disease

This report describes Parkinson disease 1 (PARK1), which is a subtype of Parkinson disease; PARK1 exhibits autosomal dominant inheritance. The human gene implicated in this disease, SNCA (α-synuclein), encodes a protein that is abundant in neurons, including the brain. It appears to play several roles, including regulation of synaptic vesicle trafficking and subsequent neurotransmitter release. α-synuclein protein is the primary structural component of the Lewy body aggregates typically found in the brains of patients with Parkinson disease and Lewy body dementia. The SCNA gene is also associated with Parkinson disease 4 (OMIM:605543, FBhh0000007) and Lewy body dementia (OMIM:127750, FBhh0001043)

No gene orthologous to SNCA has been identified in Drosophila.

In vitro and in vivo studies, including in Drosophila, have shown that α-synuclein monomers can be sequentially assembled into several conformations, including oligomers, protofibrils, fibrils, and large aggregates of fibrils (as in Lewy bodies). In multiple different assays, the soluble oligomeric or protofibrillar forms of α-synuclein appear to be more toxic than the mature fibril forms (reviewed in FBrf0228930, FBrf0236174). The large aggregates observed as cellular inclusions, one of the histological features of Parkinson pathology, appear to represent protective (at least initially) sequestrations of the more toxic soluble forms. There is evidence that the oligomeric α-synuclein species can spread between cells, exhibiting a prion-like capacity.

Multiple different UAS constructs of the human Hsap\SNCA gene have been introduced into flies, including wild-type SNCA and genes carrying mutational lesions implicated in PARK1. Phenotypic assays using the human gene have allowed characterization of genetic interactions with candidate fly genes and transgenic human genes. Therapeutic drug candidates and classes of deleterious compounds have been administered by feeding and tested using several different phenotypic assays.

Variant(s) implicated in human disease tested (as transgenic human gene, SNCA): A30P, E46K, H50Q, G51D, and A53T variant forms of the human gene have been introduced into flies. The E46K variant is also implicated in Lewy body dementia (FBhh0001043).

[updated Mar. 2019 by FlyBase; FBrf0222196]

Disease Summary Information
Parent Disease Summary: Parkinson disease
Symptoms and phenotype

Parkinson disease (PD) is a neurodegenerative disease usually typified by slow onset in mid to late adulthood; there are also early-onset and juvenile forms of the disease. Symptoms worsen over time and include resting tremor, muscular rigidity, bradykinesia [abnormal slowness of movement], and postural instability [impaired balance and coordination]; additional symptoms may include postural abnormalities, dysautonomia [symptoms caused by malfunction of the autonomic nervous system], dystonic cramps, and dementia. Parkinson disease is the second-most common neurodegenerative disease (after Alzheimer disease), affecting approximately 1% of the population over 50 (Polymeropoulos et al., 1996, pubmed:8895469). [from OMIM:168600; 2013.07.23]

Parkinson disease is described as early-onset disease if signs and symptoms begin before age 50. Early-onset cases that begin before age 20 may be referred to as juvenile-onset disease. [from Genetics Home Reference, GHR_condition:parkinson-disease, 2015.02.13]

Specific Disease Summary: Parkinson disease 1
OMIM report


Human gene(s) implicated


Symptoms and phenotype

Parkinson disease 1 and Parkinson disease 4 are characterized by typical symptoms of Parkinson disease (described above). Both are frequently associated with relatively early onset, rapid progression, cognitive decline, and high levels of penetrance. [from OMIM:168600, OMIM:168601 and OMIM:605543; 2015.02.16]


PARK1 and PARK4 both exhibit autosomal dominant transmission; both are caused by mutations in the SNCA gene, which encodes alpha-synuclein (Polymeropoulos, et al., 1996, pubmed:9197268). Mutations implicated in Parkinson disease include A53T and A30P (multiple references cited in OMIM:163890). Familial pedigrees with duplications or triplications of the SNCA gene have been described; they exhibit varied Parkinson phenotypes and penetrance. It has been postulated that alterations in SNCA gene dosage due to rearrangements may be more common than point mutations (Ibanez et al., 2009, pubmed:19139307). [from OMIM:168601, OMIM:163890 and OMIM:605543; 2015.02.16]

Cellular phenotype and pathology

At autopsy, SNCA-positive Lewy body protein aggregates are observed within neurons in multiple areas of the brain. [from OMIM:168601; 2015.02.16]

Molecular information

Alpha-synuclein is a highly conserved protein that is abundant in neurons, especially in presynaptic terminals. [from OMIM:163890; 2015.02.16]

The SNCA protein plays several roles in synaptic activity such as regulation of synaptic vesicle trafficking and subsequent neurotransmitter release. It participates as a monomer in synaptic vesicle exocytosis by enhancing vesicle priming, fusion, and dilation of exocytotic fusion pores. It also acts also as a molecular chaperone in its multimeric membrane-bound state, assisting in the folding of SNARE synaptic fusion components at presynaptic plasma membrane; this chaperone activity is important to sustain normal SNARE-complex assembly during aging. [Gene Cards, SNCA; 2019.06.03]

External links
Disease synonyms
Parkinson's disease
Parkinson disease
Parkinson disease 1, autosomal dominant
Parkinson disease 1, autosomal dominant Lewy body
Search term: synucleinopathy
Ortholog Information
Human gene(s) in FlyBase
Human gene (HGNC)
D. melanogaster ortholog (based on DIOPT)
Comments on ortholog(s)

No gene orthologous to SNCA has been identified in Drosophila.

Other mammalian ortholog(s) used
    D. melanogaster Gene Information (0)
    Other Genes Used: Viral, Bacterial, Synthetic (0)
      Summary of Physical Interactions (4 groups)
      Interacting group
      anti bait coimmunoprecipitation, western blot
      colocalization, fluorescence microscopy, inferred by author
      anti bait coimmunoprecipitation, western blot
      anti bait coimmunoprecipitation, western blot
      Alleles Reported to Model Human Disease (Disease Ontology) (29 alleles)
      Models Based on Experimental Evidence ( 29 )
      Modifiers Based on Experimental Evidence ( 12 )
      Alleles Representing Disease-Implicated Variants
      Genetic Tools, Stocks and Reagents
      Sources of Stocks
      Contact lab of origin for a reagent not available from a public stock center.
      Bloomington Stock Center Disease Page
      Selected mammalian transgenes
      Publicly Available Stocks
      Selected Drosophila transgenes
      Publicly Available Stocks
      RNAi constructs available
      Publicly Available Stocks
      Selected Drosophila classical alleles
      Allele class
      Publicly Available Stocks
      References (228)