The human SNCAIP gene appears to be implicated in the development of or susceptibility to late-onset Parkinson disease. The SNCAIP protein (synphilin‐1) has been shown to interact with the protein encoded by SNCA (alpha-synuclein), which is implicated in Parkinson disease 1 (FBhh0000006). Alpha-synuclein is a major component of Lewy bodies identified in the brains of Parkinson disease patients; synphilin-1 has also been shown to be present in Lewy bodies.
In Drosophila, there is no identified ortholog of either SNCAIP or SNCA.
Multiple UAS constructs of the wild-type human Hsap\SNCAIP gene have been introduced into flies. Panneuronal expression of the Hsap\SNCAIP transgene results in progressive loss of locomotor activity, shortened lifespan and retinal damage. These phenotypes are very similar to those obtained for panneuronal expression of Hsap\SNCA transgenes (wild-type or SNCA disease-implicated variants). A key and unexpected finding is that panneuronal coexpression of Hsap\SNCAIP with a Hsap\SNCA gene carrying a disease-implicated variant results in normal locomotor activity and lifespan. These results support the hypothesis that imbalance in the ratio of alpha-synuclein and synphilin‐1 is highly deleterious for dopaminergic neurons. Expression of Hsap\SNCAIP is also associated with progressive loss of response to olfactory stimuli in adult flies; this mirrors the loss of smell that often occurs early in the progression of Parkinson disease.
This model has been used to investigate nicotine as a possible therapeutic intervention during early stages of Parkinson disease.
[updated May 2021 by FlyBase; FBrf0222196]
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 MIM: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]
SNCAIP encodes synphilin‐1, a protein containing several protein-protein interaction domains, including ankyrin-like repeats, a coiled-coil domain, and an ATP/GTP-binding motif. The encoded protein interacts with alpha-synuclein (SNCA) in neuronal tissue and may play a role in the formation of cytoplasmic inclusions and neurodegeneration. [Gene Cards, SNCAIP; 2012.05.18]
Synphilin-1 has been shown to be present in Lewy bodies of Parkinson disease patients (Wakabayashi et al., 2000; pubmed:10762166).
No orthologous gene in Drosophila has been identified.
