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
HTRA2	Missense	..	Unclear	Dominant
ATP13A2	Missense or loss of function	Atypical PD	Loss of function	Recessive
FBXO7	Missense	Often early onset	Loss of function	Recessive
GIGYF2	Missense	..	Unclear	Dominant
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
EIF4G1	Missense	..	Unclear	Dominant
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)

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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.

Reference

Deng, H.; et al. The genetics of Parkinson disease. Ageing Res Rev. 2018, 42: 72-85.

For Research Use Only. Not For Clinical Use.

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PD In Vitro Disease Models

Targets and Mutations Involved in PD

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