Synaptic Plasticity/Neuroprotection Targeting Therapies Study

Background of Synaptic Plasticity/Neuroprotection Targeting Therapies Study

The normal function of synapses is fundamental to central nervous system. Although the pathogenic mechanisms of Alzheimer's disease (AD) associated with amyloid and pathologic tau have been elucidated and applied to the development of relevant targeted drugs, synaptic deficiency and dysfunction should also be addressed. Synaptic integrity is directly driven by amyloid plaque and tau aggregation pathology at the prodromal stage before AD clinical manifestations oncome. After a long-term pathologic process, synaptic plasticity and synaptic density are affected by the interaction between neurodegeneration and atrophy, which aggravate AD progression. Synaptic and neuroplastic mechanisms of action (MoAs) represent a potential opportunity for the treatment of AD. Synaptic plasticity targeting therapies attempt to restore and maintain the synaptic normal function as well as optimize cognitive ability. There have been several approaches targeting synapses, including anti-cholinesterase's, selective serotonin reuptake inhibitors, and NMDA antagonists. Creative Biolabs offers a full range of in vivo, in vitro, and ex vivo assays for synaptic plasticity and neuroprotection targeting therapies studies, enabling researchers to understand the synaptic plastic MoA in AD, and thereby diving preclinical drug development targeting synapses.

Synaptic Plasticity/Neuroprotection MoA in AD

Synaptic plasticity refers to the capability of the synapses to dynamically modulate the function in response to internal or external alterations. The β-amyloid (Aβ) and hyperphosphorylated tau proteins are the two main pathological hallmarks of AD, which contribute to the accumulation of extracellular amyloid plaques and intracellular neurofibrillary tau tangles. However, transportation of the soluble Aβ oligomers and tau oligomers to synapses appears to be more toxic to the synaptic function and density. Soluble Aβ oligomers enhance DKK1 levels, which activate non-canonical signaling causing loss and disintegration of synapses. Soluble hyperphosphorylated tau species and oligomers enter post-synapses destroying long-term potentiation through regulating Fyn/NMDAR complexes, which modulate the normal function of synapses through the impairments of mitochondria, synaptic vesicle mobility, and neurotransmitter release. Soluble Aβ and tau will also trigger a range of neuroinflammation by activating glia and subsequent accumulation will exacerbate synaptic loss and dysfunction as well as neurodegeneration.

Fig.1 Disruption of neuronal plasticity may occur via several mechanisms. (Jackson, 2019)

Related Services at Creative Biolabs

Synaptic plasticity and neuroprotection targeting therapies study services provided by Creative Biolabs can comprehensively fulfill your research and drug development requirements. You can get access to our neuronal plasticity assays including neurogenesis assay, synaptogenesis assay, and neurite outgrowth or degeneration assay. Our platforms with high-throughput techniques enable researchers to visualize synaptic dynamics at the first glance. If you have the intention to study synaptic plasticity and neuroprotection in AD, please don't hesitate to contact us. We are ready to answer questions about relevant expertise and assist you to design the optimal solution.

Reference

1. Jackson, J.; et al. Targeting the synapse in Alzheimer's disease. Frontiers in neuroscience. 2019, 13: 735.