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Neurodegenerative disease and male infertility

Neurodegenerative Biomarkers: 4BioDx has a range of monoclonal and polyclonal antibodies specific for several tau proteins and APP (amyloid protein precursors), which are important biomarkers in the investigation of the underlying processes of neurodegenerative diseases.

Male Infertility: 4BioDx have a range of ELISA kits, monoclonal and polyclonal antibodies for the investigation of male infertility, specifically targeting proAKAP4 (A-kinase anchor protein 4), an important biomarker of sperm motility.

Alzheimer’s Disease and the role of Tau proteins and APP (amyloid protein precursors)

Anti-Phospho Tau Antibodies as biomarkers in neurodegenerative diseases: Microtubule-associated Tau proteins regulate polymerization and stability of microtubules through their microtubule-binding domains and their level of phosphorylation.

In Alzheimer’s disease and related disorders, these tau proteins aggregate into filaments. Tau proteins in these filaments are phosphorylated. Most of the phosphorylation sites are also found in physiological conditions. However, the phospho-Ser422 is considered as an abnormal site of phosphorylation and is found in several diseases with neurofibrillary degeneration (Bussière et al. 1999). This phospho-Ser422 is correlated with the severity of neuronal pathology in Alzheimer’s disease (Augustinack et al. 2002) and is also an epitope encountered in numerous Tau transgenic mouse models. With such characteristics, this epitope has also been targeted in many immunotherapy approaches (Troquier et al. 2012 ; Collin et al. 2014).

Anti-phospho APP antibodies as biomarkers in neurodegenerative diseases: Beta-amyloid precursor protein (APP) is a well-conserved and ubiquitous 100-140 kDa transmembrane glycoprotein that exists as several isoforms and is strongly implicated in the pathogenesis of Alzheimer’s disease. APP and APP family members APLP1 and APLP2 functions still remains elusive, but they are clearly implicated in neuronal development, signaling, intracellular transport, iron homeostasis and other aspects of neuronal homeostasis (Van der Kant and Goldstein, 2015).

APP metabolism leads to the production of amyloid-beta peptides that are the main components of amyloid deposits in Alzheimer’s disease. Amyloid-beta peptides (Ab) are produced following by sequential cleavages of APP by proteases (called secretases). APP processing by secretases produce the carboxy-terminal fragments (CTFs) among which the beta-carboxy-terminal fragments are the substrates of the gamma-secretase to produce amyloid-beta peptides.

The Importance of AKAP4 in male infertility

AKAP4 (A-kinase anchor protein 4) plays a central role in flagellar structure, chemotaxis, capacitation and in sperm motility. In mammals, AKAP4 is expressed during spermatogenesis. This 854 amino-acid protein is processed from a pro-AKAP4 (854 aa) to a “mature” AKAP4 protein lacking the first 188 amino acids. AKAP4 is specifically localised to the fibrous sheath of the principal piece of the flagellum, a structure involved in flagellum structure and sperm motility.
 
AKAP4 (also named AKAP82) is a one of the major components (~50%) of the sperm fibrous sheath. The AKAP4 precursor termed proAKAP4 is processed to mature AKAP4 during sperm maturation in the testes. In humans, the AKAP4 gene is located on the X chromosome.
 
In the literature, AKAP4 was previously named AKAP82, PRKA4 (Protein Kinase A Anchoring Protein 4), CT99 (Cancer/Testis Antigen 99), HI, p82, or FSC1 (Fibrous Sheath Component 1). AKAP4 protein belongs to the family of A-kinase anchor proteins (AKAPs) all sharing a common function of binding to the regulatory subunit of protein kinase A (PKA) and confining the PKA holoenzyme to discrete locations within the cell. Therefore, AKAP4 is an essential regulator of PKA and PKC protein kinases signalling to the motor protein dynein of the axoneme of the flagellum.