Calcium Targeting Therapies Study

As a reputable bio-innovation company in the field of neuroscience, Creative Biolabs has been committed to providing custom development services such as establishing custom animal models, developing and screening suitable calcium channel blockers to help you gain a deep understanding of Parkinson's disease (PD) mechanism of action (MoA).

Vital Roles of Calcium

Among various life activities, calcium is an important factor that cells use to respond to changing environments. As we all know, calcium acts as a central regulator in fertilization and development. Furthermore, calcium is a major second messenger, which plays a crucial role in the biochemical mechanisms and transmits depolarization status and synaptic activity to neurons. Calcium signaling affects all aspects of neuronal cell biology, therefore, cells must tightly regulate calcium levels to avoid uncontrolled responses that can lead to pathological conditions and cell death. Thus, calcium regulation becomes a key process in neurons, which have developed extensive and complex calcium signaling pathways.

Calcium and PD

PD is one of the most common neurological disorders in humans and is characterized by the aggregation of the α-synuclein protein. Evidence shows that neuronal calcium signaling is abnormal in many neurodegenerative diseases. Furthermore, an emerging key pathological feature caused by α-synuclein aggregation is the disruption of calcium homeostasis. Therefore, an in-depth exploration of the role of abnormal neuronal calcium signaling in PD may provide new directions for developing effective therapeutic strategies to combat these devastating neurological diseases.

Fig.1 Key events in the aging model of PD. (Surmeier, et al., 2007)

Calcium Targeting Therapies for PD

The motor symptoms of PD are due to the progressive loss of dopamine (DA) neurons in the substantia nigra pars compacta (SNc). Currently, no strategy can effectively slow the progression of the disease, so it is necessary to identify potential neuroprotective agents. The pathogenesis of PD involves calcium flux and overload, which sheds new light on calcium regulation as a possible therapeutic target. L-type calcium channels (LTCCs) located on the plasma membrane of dopaminergic cells are responsible for extracellular to intracellular calcium flux. These LTCCs can be inhibited by dihydropyridine calcium channel blockers (DiCCB). In PD animal models, treatment with DiCCB has been found to reduce toxin-induced loss of substantia nigra dopaminergic cells and prevent toxin-induced motor deficits. In addition, other LTCCs antagonists have also shown neuroprotective potential, such as isradipine.

Creative Biolabs has been a long-term expert in the field of central nervous system disease research. With our extensive experience and advanced platforms, we are confident in providing comprehensive services for calcium MoA research, from animal model establishment to final data analysis. If you are interested in our services, please feel free to contact us for more details.

Reference

1. Surmeier, D. J.; et al. Calcium, aging, and neuronal vulnerability in Parkinson's disease. The Lancet Neurology. 2007, 6(10): 933-938.