Neuroscience is the study of the structure and function of the nervous system. On a broad scale this includes the brain and the peripheral nervous system and how they work together to regulate movement, behavior, and cognition. On a smaller scale, neuroscience focuses on individual cell types or proteins that promote memory formation, retention, and retrieval. There is also an intense focus on therapeutic development for various neurological disorders.
Competitive ELISA for activity of Class I PI3-K via detection of the reaction product PIP3.
Monoclonal antibody for the detection of the phosphoinositide PI(4,5)P2.
Tet On/Off system agonist that acts on tetracycline responsive promoters.
The predominant form of β-amyloid protein found in the brains of patients with Alzheimer′s disease.
Neuroscience can be approached from several different levels, but from a molecular and cellular perspective the fundamental units of neuroscience are the neuron and the connections between neurons, called synapses. These specialized structures form the basis of communication between neurons and are widely accepted to contain the molecular machinery for memory formation.
The distribution and type of lipids in the pre and post-synaptic membranes are critical for maintaining proper function. Cholesterol, sphingolipids, and certain phosphoinositides all play roles in regulating neurotransmitter release, receptor trafficking, and ultrastructural changes.
At any given synapse there are myriad signaling pathways that are connected and active with various receptors. Two of the most studied receptor groups are the glutamate and neurotrophin (NT) receptors.
The two predominant glutamate receptor types are AMPARs and NMDARs. These receptors work in tandem to regulate the excitability of the post-synaptic membrane and the signaling cascade that runs through calmodulin kinase II (CaMKII), which regulates transcription of key genes for memory formation, aka synaptic plasticity.
As their name implies, NT receptors bind to a family of proteins and peptides called neurotrophins. These receptors activate a series of signaling pathways, including the PKC and PI3K pathways, which collectively support differentiation and survival of neurons, but also participate in synaptic plasticity.
A large portion of neuroscience research has been defined by the need to address neuropsychiatric and neurodegenerative (ND) disorders. ND includes several different diseases such as Alzheimer’s, Parkinson’s, Huntington’s, and amyotrophic lateral sclerosis, which are detrimental to motor and memory functions in the central nervous system to varying degrees.
A shared hallmark of all of these disorders is the formation of presumably toxic protein aggregates. The most well known of these are amyloid beta (Aβ) aggregates, or plaques. The normal physiological functions of Aβ have been elusive, with research pointing to a range of possible functions including promotion of synaptic plasticity and antimicrobial activity. Conversely, Aβ aggregates or abnormally high levels of Aβ have been reported to be deleterious to neurons.
Due to these observations, therapeutic avenues for Alzheimer’s disease have focused almost exclusively on modulating levels of Aβ. Early efforts focused on inhibiting the cellular machinery that produced Aβ peptide fragments while more recent approaches have utilized monoclonal antibodies that selectively bind Aβ aggregates.