PD Mechanism of Action (MoA) Studies

Background of Parkinson's Disease Studies

Parkinson's disease (PD) is the second prevalent progressive neurodegenerative disease associated with population aging, causing unintended or uncontrollable movements. The onset of PD is mainly caused by the gradual degeneration and loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) that subsequently reduce dopamine levels. Currently, no effective treatment can either directly retard dopaminergic neurodegeneration, or prevent the progression of PD. Thus, the requirement for more effective therapies is urgent and critical. Understanding the molecular signaling pathways participating in PD will help the developers to reveal the mysteries of the disease and thereby explore emerging therapies. Creative Biolabs offers advanced technologies and platforms as well as reliable professional targeting study services that can meet any requirements in research and preclinical drug development for PD.

PD Mechanism of Action

The mechanisms of action (MoAs) in PD are complicated. Both genetic and environmental factors are involved in PD. The primary MoAs involved in PD encompass aggregation of misfolded proteins, such as α‐synuclein and hyperphosphorylated tau protein, dysfunction of the ubiquitin-proteasome pathway for the protein clearance, genetic mutations, loss and dysfunction of mitochondria, oxidative stress, excitotoxicity, and neuroinflammation.

The mitochondrial function is affected by aging, environmental toxins, as well as gene mutation (DJ-1, PINK1, and LRRK2). Dysfunction of mitochondria leads to bioenergy failure and oxidative stress with elevated reactive oxygen species (ROS), which aggravate tau phosphorylation and neuroinflammation. The mutation of the α‐synuclein gene leads to the aggregation of α‐synuclein. The mutation of parkin and UCHL1 alters the ubiquitin-proteasome system and affects the autophagy lysosomal pathway, which impairs the function of misfolded protein degradation, causing the aggregation of pathological tau and α‐synuclein to form Lewy bodies. Lewy bodies and bioenergetic depletion ultimately cause the degeneration of dopaminergic neurons. As a consequence, there is an urgent need to develop therapies that inhibit α‐synuclein misfolding and aggregation, increase α‐synuclein degradation, targe LRRK2 gene mutation and glucocerebrosidase, as well as target iron and calcium, etc. In addition, cell-replacement therapies, neurotrophic therapies, and gene therapies are new ways of thinking used in PD treatment.

Fig.1 Potential neuroprotective mechanisms of novel targeted therapies in Parkinson's disease. (Ntetsika, et al., 2021)

Creative Biolabs has a long-term dedication to neuroscience translational studies. We offer a full range of in vivo, in vitro, and ex vivo assays with multiple types of stable cell culture models as well as transgenic and aged animal models. Our advanced technologies including high-throughput imaging and electrophysiology tools and behavioral testing platforms allow a large amount of high-quality data to be applied in the PD mechanism of action studies. Understanding the MoAs in PD assists the developers to explore novel targets and screening promising compounds for delaying the PD progress or restoring the cognitive function. To learn more about the PD MoA studies, please don't hesitate to contact us. Our neuroscience experts are pleased to provide you with customized solutions.

For further details about PD MoA studies, please check out the following links:

• Alpha-synuclein Targeting Therapies Study
• LRRK2 Targeting Therapies Study
• Calcium Targeting Therapies Study
• Iron Targeting Therapies Study
• Cell‐Replacement Therapies Study
• Neurotrophic Factors Therapies Study
• Gene Therapies Study
• Glucocerebrosidase Targeting Therapies Study

Reference

1. Ntetsika, T.; et al. Novel targeted therapies for Parkinson's disease. Molecular Medicine. 2021, 27(1): 1-20.