Drug Addiction It is commonly known that drug addiction involves permanent synaptic plasticity of various neuronal circuits.<unk>  is being applied to study the effect of drug addiction across the synapse. Research is being conducted by isolating distinct regions of the brain in which synaptic transmission takes place and defining the proteome for that particular region. Different stages of drug abuse must be studied, however, in order to map out the progression of protein changes along the course of the drug addiction. These stages include enticement, ingesting, withdrawal, addiction, and removal. It begins with the change in the genome through transcription that occurs due to the abuse of drugs. It continues to identify the most likely proteins to be affected by the drugs and focusing in on that area. For drug addiction, the synapse is the most likely target as it involves communication between neurons. Lack of sensory communication in neurons is often an outward sign of drug abuse, and so<unk>  is being applied to find out what proteins are being affected to prevent the transport of neurotransmitters. In particular, the vesicle releasing process is being studied to identify the proteins involved in the synapse during drug abuse. Proteins such as synaptotagmin and synaptobrevin interact to fuse the vesicle into the membrane. Phosphorylation also has its own set of proteins involved that work together to allow the synapse to function properly. Drugs such as morphine change properties such as cell adhesion, neurotransmitter volume, and synaptic traffic. After significant morphine application, tyrosine kinases received less phosphorylation and thus send fewer signals inside the cell. These receptor proteins are unable to initiate the intracellular signaling processes that enable the neuron to live, and necrosis or apoptosis may be the result. With more and more neurons affected along this chain of cell death, permanent loss of sensory or motor function may be the result. By identifying the proteins that are changed with drug abuse,<unk>  may give clinicians even earlier biomarkers to test for to prevent permanent neurological damage. Recently, a novel terminology (Psychoproteomics) has been coined by the University of Florida researchers from Dr. Mark S Gold Lab. Kobeissy et al. defined Psychoproteomics as integral proteomics approach dedicated to studying proteomic changes in the field of psychiatric disorders, particularly substance-and drug-abuse neurotoxicity. Brain Injury Traumatic brain injury is defined as a “direct physical impact or trauma to the head followed by a dynamic series of injury and repair events”. Recently,<unk>  have been applied to studying the disability that over 5.4 million Americans live with. In addition to physically injuring the brain tissue, traumatic brain injury induces the release of glutamate that interacts with ionotropic glutamate receptors (iGluRs). These glutamate receptors acidify the surrounding intracranial fluid, causing further injury on the molecular level to nearby neurons. The death of the surrounding neurons is induced through normal apoptosis mechanisms, and it is this cycle that is being studied with<unk> . Three different cysteine protease derivatives are involved in the apoptotic pathway induced by the acidic environment triggered by glutamate. These cysteine proteases include calpain, caspase, and cathepsin. These three proteins are examples of detectable signs of traumatic brain injury that are much more specific than temperature, oxygen level, or intracranial pressure. Proteomics thus also offers a tracking mechanism by which researchers can monitor the progression of traumatic brain injury, or a chronic disease such as Alzheimer’s or Parkinson’s. Especially in Parkinson’s, in which neurotransmitters play a large role, recent proteomic research has involved the study of synaptotagmin. Synaptotagmin is involved in the calcium-induced budding of vesicle containing neurotransmitters from the presynaptic membrane. By studying the intracellular mechanisms involved in neural apoptosis after traumatic brain injury, researchers can create a map that genetic changes can follow later on. Nerve Growth One group of researchers applied the field of<unk>  to examine how different proteins affect the initial growth of neuritis. The experiment compared the protein activity of control neurons with the activity of neurons treated with nerve growth factor (NGF) and JNJ460, an “immunophilin ligand.” JNJ460 is an offspring of another drug that is used to prevent immune attack when organs are transplanted. It is not an immunosuppressant, however, but rather it acts as a shield against microglia. NGF promotes neuron viability and differentiation by binding to TrkA, a tyrosine receptor kinase. This receptor is important in initiating intracellular metabolic pathways, including Ras, Rak, and MAP kinase. Protein differentiation was measured in each cell sample with and without treatment by NGF and JNJ460. A peptide mixture was made by washing off unbound portions of the amino acid sequence in a reverse column. The resulting mixture was then suspended a peptide mixture in a bath of cation exchange fluid. The proteins were identified by splicing them with trypsin and then searching through the results of passing the product through a mass spectrometer. This applies a form of liquid chromatography mass spectrometry to identify proteins in the mixture JNJ460 treatment resulted in an increase in “signal transduction” proteins, while NGF resulted in an increase in proteins associated with the ribosome and synthesis of other proteins. JNJ460 also resulted in more structural proteins associated with intercellular growth, such as actin, myosin, and troponin. With NGF treatment, cells increased protein synthesis and creation of ribosomes. This method allows the analysis of all of the protein patterns overall, rather than a single change in an amino acid. Western blots confirmed the results, according to the researchers, though the changes in proteins were not as obvious in their protocol. The main significance to these findings are that JNJ460 are NGF are distinct processes that both control the protein output of the cell. JNJ460 resulted in increased neuronal size and stability while NGF resulted in increased membrane proteins. When combined, they significantly increase a neuron’s chance of growth. While JNJ460 may “prime” some parts of the cell for NGF treatment, they do not work together. JNJ460 is thought to interact with Schwann cells in regenerating actin and myosin, which are key players in axonal growth. NGF helps the neuron grow as a whole. These two proteins do not play a part in communication with other neurons, however. They merely increase the size of the membrane down which a signal can be sent. Other neurotrophic factor proteomes are needed to guide neurons to each other to create synapses.
Neuroproteomics
Viral neuronal tracing
Brain fingerprinting
Luria-Nebraska neuropsychological battery
Iatrochemistry
Clinical neurochemistry
Addenbrooke's Cognitive Examination
Watson–Schwartz test