Neuroscience

Neurofibromatosis (NF) is a genetic disorder caused by mutations in the NF1, NF2 or SMARCB1 genes which lead to tumor growth on nerves throughout the body. Although the tumors are usually benign, they still require chemotherapy to shrink and may become cancerous. Surgery is often attempted as treatment, however tumor placement on sensitive areas such as spinal cord and optic nerve make this option more difficult.

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Mannose 6 phosphate (M6P) is a sequence tag that plays a pivotal role in transporting proteins from the Golgi complex and cell surface to the lysosome. The M6P sequence is tagged to the N-linked oligosaccharides of lysosomal hydrolases as they traverse the cis-Golgi apparatus. Upon M6P-tagging, these proteins are targeted to the late endosome via vesicular transport. Low pH conditions there mediate the dissociation of a M6P Receptor from its ligand, allowing recycling of the M6P sequences.

Nitric oxide (NO) is an inorganic, gaseous, and reactive free radical that acts as a biologic mediator in processes such as neurotransmission, vasorelaxation, and cytotoxicity. In addition, it has antimicrobial and anti-tumoral activities. NO production is mediated by members of the nitric oxide synthase (NOS) family. The NOS enzyme catalyzes the oxidization of L-arginine into L-citrulline and NO.  Several subtypes have been identified: two constitutive isoforms (type I brain/neuronal NOS, and type III endothelial) and one inducible isoform (iNOS, or type II).

The protein CD11b has been implicated in the various adhesion-related interactions of cells such as monocytes, macrophages, natural killer (NK) cells, and granulocytes. It is part of a heterodimer that consists of CD11b and CD18. It also modulates the uptake of complement-coated particles within the cell. It is commonly used as a microglial marker in tissues derived from the nervous system.

Amyotrophic lateral sclerosis is a neurological disease which impacts motor neurons that are involved in muscle movement throughout the body. The progressive degeneration of neurons causes weakened muscles and can lead to paralysis. There is no cure for ALS, but riluzole has been used to help with the damage to the motor neurons.

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The cluster of differentiation 4 (CD4) protein is a surface, type I membrane-embedded glycoprotein that is found on a wide range of cells: T-lymphocytes, B-cells, macrophages, granulocytes, and developmentally-dependent regions specific to the brain. It interacts with major histocompatibility complex (MHC) class II anti-genes, serves as the human immunodeficiency virus (HIV) receptor, and can initiate/augment early phase T-cell activation.  In immune-mediated and central nervous system (CNS) infectious diseases, CD4 indirectly mediates neuronal damage.

C9RANT is a newly discovered protein-like chain that holds great potential promise as a benchmark for measuring disease activity and therapeutic response for patients with the devastating conditions of amyotrophic lateral sclerosis (ALS) and dementia. Mutations within a non-coding region of the C9ORF72 gene are responsible for 20-40% of cases of familial ALS¹. This class of mutations generates repetitive, high molecular weight RNA chains which are insoluble and aggregate within the brain as C9RANT accumulations.

The protein ATF6 is a constitutively expressed transcription factor that is a key mediator of the unfolded protein response (UPR) that allows mammalian cells to maintain cellular homeostasis under conditions of environmental and physiological stress. ATF6 is endoplasmic reticulum (ER) membrane-anchored in its inactive form, and under certain stress conditions, translocates to the Golgi where it is processed into its active form through action of the S1P and S2P proteases.

LOX is a copper-dependent amine oxidase enzyme that executes post-translational oxidative deamination on peptidyl lysine residues in precursors of fibrous collagen and elastin. LOX is secreted into the extracellular environment in an inactive form, where it is processed into an active form. Its activity is crucial for maintaining both the tensile and elastic properties of connective tissue residing within skeletal, pulmonary, and cardiovascular systems.

In the synthesis pathway for the catecholamines - dopamine, epinephrine, and norepinephrine, tyrosine hydroxylase is the rate-limiting enzyme. Through alternative mRNA splicing, a wide molecular diversity of TH isoforms are generated that are tissue-specific and carry varied enzymatic activities, allowing for differential neurotransmitter availability at various synapses.