Parkinson’s disease models
Mouse models for Parkinson’s disease (PD) mimic different aspects of the disease, such as substantia nigra degeneration, alpha-synuclein pathology, and dysfunction of intracellular pathways.
Parkinson’s disease is a neurodegenerative disorder that affects the motor systems in early stages, leading to symptoms such as trembling, slowing of movement, and muscle stiffness. PD is also associated with autonomic nervous system and neuropsychiatric problems. Although there are several therapies available to treat the symptoms of PD, no treatments are available that halt the disease progression.
MPTP-based inducible models
Degeneration of dopaminergic cells in the substantia nigra (SN) is the primary cause of the motor symptoms in Parkinson’s disease (PD). MPTP is a pro-drug for the neurotoxin MPP+, which selectively kills dopamine-producing neurons in the SN. Administration of MPTP to mice is one of the most widely used mouse models of PD. Sylics has detected loss of dopaminergic SN neurons, motor impairment, and activation of the NLRP3 inflammasome in the MPTP mouse model.
Transgenic alpha-synuclein model
Alpha-synuclein (α-syn) inclusions are the main histopathological hallmark of Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and multiple systems atrophy (MSA). Cellular aggregates in these synucleinopathies closely correlate with the disease progression. Mutations in the α-syn encoding gene are also associated with both familial and sporadic forms of PD. Pathological α-syn is therefore thought to play a key role in the disease pathogenesis. Sylics offers free-for-service transgenic α-syn mouse models, which recapitulate the α-syn aggregates found in PD, DLB, and MSA.
Alpha-synuclein seeding models
Alpha-synuclein (α-syn) pathology progresses through the brain and closely correlates with disease symptoms. It is increasingly recognized that transneuronal spreading α-syn pathology plays a key role in the pathophysiology of Parkinson’s disease and other synucleinopathies. Injection of brain extracts from these diseases in the brain of mice closely mimics the structural features of the α-syn aggregates found in patients and allows studying of α-syn spreading as a therapeutic readout. Sylics has extensive experience with seeding-based mouse models, based on both recombinant and patient-derived seeds.
GBA model relevant for Gaucher's and Parkinson's disease
The GBA gene encodes for the lysosomal glucocerebrocidase enzyme that is required for the metabolism of glucocerebroside, a sphingolipid that is also known as glucosylceramide. Rare genetic mutations in GBA that disrupt metabolism of glucocerebroside are known to cause Gaucher's disease, a lysosomal storage disease that affects the function of several tissues including the brain. Sylics has profound experience with repeated or chronic intra-ventricular infusions to test new enzyme replacement therapies (ERT) in GBA mouse models. Furthermore, mutations in GBA are associated with both familial and sporadic forms of Parkinson’s disease. Mouse models that express GBA with PD-associated mutations are therefore attractive models for studying therapeutics that target intracellular lysosomal pathways for the treatment of PD.
Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene, which encodes a kinase with a multitude of cellular functions (e.g. lysosomal function), are associated with both familial and sporadic forms of Parkinson’s disease. Inhibition of LRRK2 is increasingly pursued as a therapeutic strategy in PD. Mouse models that express human LRRK2 with PD-associated mutations are therefore an attractive model for studying therapeutics that target this protein. Sylics offers free-for-service LRRK2 mutation mouse models.
6-OHDA lesion model
Degeneration of dopaminergic cells in the substantia nigra (SN) is the primary cause of the motor symptoms in Parkinson’s disease (PD). Oxidopamine or 6-OHDA is a neurotoxin which selectively kills dopamine-producing neurons in the SN. Injection of rodents with 6-OHDA is a widely used mouse model of PD. This model is particularly robust in rats. Sylics has extensive experience with the administration of neurotoxic compounds as mouse models of PD.
Please reach out to us if you want to learn more about our Parkinson’s disease models solutions. We will contact you within 1 business day.