Brain Molecular Pathways

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• Ligand-gated ion channels
  • AMPA receptors
  • NMDA receptors
  • 5-HT3 receptors
  • GABA receptors
  • Nicotinic acetylcholine receptors
• Voltage-gated ion channels
  • Calcium-activated potassium channels
  • CatSper and Two-Pore channels
  • Cyclic nucleotide-regulated channels
  • Inwardly rectifying potassium channels
  • Transient Receptor Potential channels
  • Two-P potassium channels
  • Voltage-gated calcium channels
  • Voltage-gated potassium channels
  • Voltage-gated sodium channels
• Nucleosides
  • cAMP
• Synaptic Kinases
  • PKA
  • CaMKII
• Transcription Factors
  • CREB
• Promoter Genes
  • CRE
  • SARE
• Immediate Early Genes
  • cfos
  • zif
  • Arc
• G protein-coupled receptors
  • 5-Hydroxytryptamine receptors
  • Acetylcholine receptors (muscarinic)
  • Adenosine receptors
  • Adrenoceptors
  • Angiotensin receptors
  • Apelin receptor
  • Bile acid receptor
  • Bombesin receptors
  • Bradykinin receptors
  • Calcitonin receptors
  • Calcium-sensing receptors
  • Cannabinoid receptors
  • Chemerin receptor
  • Chemokine receptors
  • Cholecystokinin receptors
  • Complement peptide receptors
  • Corticotropin-releasing factor receptors
  • Dopamine receptors
  • Endothelin receptors
  • Estrogen (G protein-coupled) receptor
  • Formylpeptide receptors
  • Free fatty acid receptors
  • Frizzleds
  • GABAB receptors
  • Galanin receptors
  • Ghrelin receptor
  • Glucagon receptor family
  • Glycoprotein hormone receptors
  • Gonadotrophin-releasing hormone receptors
  • Histamine receptors
  • Hydroxycarboxylic acid receptors
  • Kisspeptin receptor
  • Leukotriene receptors
  • Lysophospholipid (LPA) receptors
  • Lysophospholipid (S1P) receptors
  • Melanin-concentrating hormone receptors
  • Melanocortin receptors
  • Melatonin receptors
  • Metabotropic glutamate receptors
  • Motilin receptor
  • Neuromedin U receptors
  • Neuropeptide FF/neuropeptide AF receptors
  • Neuropeptide S receptor
  • Neuropeptide W/neuropeptide B receptors
  • Neuropeptide Y receptors
  • Neurotensin receptors
  • Opioid receptors
  • Orexin receptors
  • Oxoglutarate receptor
  • P2Y receptors
  • Parathyroid hormone receptors
  • Peptide P518 receptor
  • Platelet-activating factor receptor
  • Prokineticin receptors
  • Prolactin-releasing peptide receptor
  • Prostanoid receptors
  • Protease-activated receptors
  • Relaxin family peptide receptors
  • Somatostatin receptors
  • Succinate receptor
  • Tachykinin receptors
  • Thyrotropin-releasing hormone receptors
  • Trace amine receptor
  • Urotensin receptor
  • Vasopressin and oxytocin receptors
  • VIP and PACAP receptors
  • Taste 1 receptors
• Nuclear Hormone Receptors
  • 1A. Thyroid Hormone receptors
  • 1B. Retinoic acid receptors
  • 1C. Peroxisome proliferator-activated receptors
  • 1D. Rev-Erb receptors
  • 1F. RAR-related orphan receptors
  • 1H. Liver X receptor-like receptors]]
  • 1I. Vitamin D receptor-like receptors]]
  • 2A. Hepatocyte nuclear factor-4 receptors
  • 2B. Retinoid X receptors
  • 2C. Testicular receptors
  • 2E. Tailless-like receptors
  • 2F. COUP-TF-like receptors
  • 3A. Estrogen receptors
  • 3B. Estrogen-related receptors
  • 3C. 3-Ketosteroid receptors
  • 4A. Nerve growth factor IB-like receptors
  • 5A. Fushi tarazu F1-like receptors
  • 6A. Germ cell nuclear factor receptors
  • 0B. DAX-like receptors
• Receptor Kinases
  • Other protein kinases
  • TK: Tyrosine kinase
  • TKL: Tyrosine kinase-like

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Brain Molecular Pathways Brain Molecular Pathways

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Arc, for activity-regulated cytoskeleton-associated protein (also known as Arg3.1), is a plasticity protein first characterized in 1995. Arc is a member of the immediate-early gene (IEG) family, a rapidly activated class of genes functionally defined by their ability to be transcribed in the presence of protein synthesis inhibitors. Arc mRNA is localized to activated synaptic sites in an NMDA receptor-dependent manner, where the newly translated protein is believed to play a critical role in learning and memory-related molecular processes. Arc is widely considered to be an important protein in neurobiology because of its activity regulation, localization, and utility as a marker for plastic changes in the brain. Along with other IEGs such as zif268 and Homer 1a, Arc is also a significant tool for systems neuroscience as illustrated by the development of the cellular compartment analysis of temporal activity by fluorescence in situ hybridization, or catFISH technique (see fluorescent in situ hybridization).

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Cyclic AMP or cAMP works by activating protein kinase A (PKA, cAMP-dependent protein kinase). PKA is normally inactive as a tetrameric holoenzyme, consisting of two catalytic and two regulatory units (C2R2), with the regulatory units blocking the catalytic centers of the catalytic units. Cyclic AMP binds to specific locations on the regulatory units of the protein kinase, and causes dissociation between the regulatory and catalytic subunits, thus activating the catalytic units and enabling them to phosphorylate substrate proteins. There are some minor PKA-independent functions of cAMP, e.g., activation of calcium channels, providing a minor pathway by which growth hormone-releasing hormone causes a release of growth hormone.

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PKA or Protein Kinase A

1. concentration of cAMP rises (e.g., activation of adenylate cyclase via GPCR-Gs)

2. cAMP molecules bind and release each PKA regulatory subunit.

3. catalytic subunits phosphorylate Ser and Thr residues

4. PKA can directly activate CREB, which binds CRE, altering the transcription

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CaMKII -- Ca2+/calmodulin-dependent protein kinases II are serine/threonine-specific protein kinases that are regulated by the calmodulin complex. CaMKII phosphorylates AMPA receptors at the P2 serine 831 site. This increases channel conductance of GluA1 subunits of AMPA receptors.

CaMKII has also been shown to aid in the process of AMPA receptor exocytosis. CaMKII activity leads to endosomal docking at the membrane.

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• Molecular Pathways
• LTP