Neurodegeneration

What is the Cellular Role of the CD11 Protein?

The CD11 protein is actually a heterodimer complex that consists of CD11b and CD18. CD11 is involved in numerous adhesion-related associations between cells such as monocytes, macrophages, natural killer (NK) cells, and granulocytes. CD11 also regulates the uptake of complement-coated particles within cells. It has also gained usage as a microglial marker for tissues derived from the nervous system.

The protein PINK1 is a mitochondrial-located serine/threonine kinase (PTK) that maintains organelle function and integrity. It not only protects organelles from cellular stress, but it also uses the selective auto-phagocytosis process for cleaning and clearing cell damage. Exner et al initially reported that, in humans, a PINK1 deficiency is linked to autosomal recessive incidences of both neurodegenerative pathology and Parkinson's Disease (PD) (1).

PINK1 (PTEN induced putative kinase 1) is a mitochondrial serine/threonine kinase which maintains mitochondrial function/integrity, provides protection against mitochondrial dysfunction during cellular stress, potentially by phosphorylating mitochondrial proteins, and is involved in the clearance of damaged mitochondria via selective autophagy (mitophagy).

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.

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.

Resources:

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.

Cell death via apoptosis is a key cellular function triggered by the cell death receptor family and their ligands which signal through downstream adaptor molecules and the caspase protease family. Among the subclass of initiator caspases that include subtypes -2, -8 and -9, caspase 9 is expressed in a variety of human tissues.

MTH1 (human MutT Homolog 1) is a purine nucleoside triphosphatase enzyme and belongs to the Nudix hydrolase family. In mammalian systems, MTH is a major detoxifier of the oxidized DNA precursors, 8-oxo-dGTP, 8-oxo-dATP, and 2-OH-dATP and prevents the misincorporation of these purine nucleoside triphosphates into DNA and the subsequent occurrence of A:T pairs to C:G and G:C to T:A pair transversions. The MTH enzyme can also hydrolyze the corresponding ribonucleotides, 8-oxo-GTP, 8-oxo-ATP, and 2-OH-ATP.