PD In Vitro Disease Models
Parkinson's disease (PD) influences numerous families around the world. Creative Biolabs is a professional neuroscience research services provider. We are devoted to offering one-stop solutions to help accelerate neuroscience research. We have advanced technologies and experienced specialists to help optimize our customers' schemes.
Targets and Mutations Involved in PD
Over the past 20 years, substantial progress has been made in identifying the genetic basis of PD. A series of studies concentrated on detecting disease-causing mutations and risk variants for PD, and various animal models of PD have significantly enhanced our understanding of the pathogenic mechanisms of this disorder. Investigation of the interactions between the protein products of causative genes can reveal the multiple pathogenic pathways and epigenetic mechanisms relevant to the development of PD, which includes alpha-synuclein accumulation, mitochondrial dysfunction, oxidative stress, impairment of dopamine release/storage, and synaptic vesicle cycle dysfunction, not limited to dopamine (DA) neurons, but activated microglia may also be related to PD. In addition to SCNA, PRKN and PINK1 as well as DJ-1 is also involved in PD pathogenesis through several pathways including oxidative injury, ubiquitin–proteasome system (UPS) dysfunction, and mitochondrial dysfunction. Furthermore, variants in GBA and other susceptibility genes markedly increase the risk for the development of PD. Standards and guidelines based on the American College of Medical Genetics and Genomics (ACMG) are crucial to distinguishing pathogenic mutations, genetic risk factors, uncertain significance variants, and benign variants.
Table 1 Mutations that have been reported to cause Parkinson's disease
|Mutation||Note||Proposed disease mechanism||Inheritance|
|SNCA||Missense or multiplication||Often with dementia||Gain of function or overexpression||Dominant|
|PRKN||Missense or loss of function||Often early onset||Loss of function||Recessive|
|UCHL1||Missense||..||Loss of function||Dominant|
|PARK7||Missense||Often early onset||Loss of function||Recessive|
|LRRK2||Missense||..||Gain of function||Dominant|
|PINK1||Missense or loss of function||Often early onset||Loss of function||Recessive|
|POLG||Missense or loss of function||Atypical PD||Loss of function||Dominant|
|ATP13A2||Missense or loss of function||Atypical PD||Loss of function||Recessive|
|FBXO7||Missense||Often early onset||Loss of function||Recessive|
|GBA||Missense or loss of function||..||Likely loss of function||Dominant (incomplete penetrance)|
|PLA2G6||Missense or loss of function||Often early onset||Loss of function||Recessive|
|VPS35||Missense||..||Loss of function||Dominant|
|DNAJC6||Missense or loss of function||Often early onset||Loss of function||Recessive|
|SYNJ1||Missense or loss of function||Often atypical PD||Loss of function||Recessive|
|DNAJC13||Missense||Same family as TMEM230||Unclear||Dominant|
|TMEM230||Missense||Same family as DNAJC13||Loss of function||Dominant|
|VPS13C||Missense or loss of function||..||Loss of function||Recessive|
|LRP10||Missense or loss of function||..||Loss of function||Dominant|
Fig.1 Main molecular pathways involved in PD. (Deng, 2018)
Services at Creative Biolabs
The human dopaminergic neuron-containing cultures have been successfully derived from induced pluripotent stem cells (iPSCs), neural stem cells (NSCs), and embryonic stem cells (ESCs) through different approaches. The fibroblast cells were reprogrammed using forced expression of Sox2, Klf4, Oct3/4, and c-Myc transcription factors. Moreover, fibroblasts were directly reprogrammed to functional induced dopaminergic neurons through culturing on microgroove and nanogroove substrates. Thus, animal models may be replaced initially by harnessing the translational value of dopaminergic neurons.
Based on targets and mutations involved in PD, Creative Biolabs provides relative engineered cell models to help accelerate PD research. As an industry-leading CRO company focusing on neuroscience research, we have a comprehensive cell culture model platform providing quality-assured PD in vitro modeling services to global clients.
If you are interested in our services, or you have any other questions, please don't hesitate to contact us for more information.
- Deng, H.; et al. The genetics of Parkinson disease. Ageing Res Rev. 2018, 42: 72-85.