Congo Red, Amyloid fibril-binding dye

Supplementary information

This supplementary information is collated from multiple sources and compiled automatically.

Choline acetyltransferase (ChAT) amyloid precursor protein (APP) and dihydrofolate reductase (DHFR) are important biological targets expressing distinct mechanical functions. ChAT is an enzyme that synthesizes the neurotransmitter acetylcholine; it is mainly expressed in the central and peripheral nervous systems. ChAT has a mass of about 69 kDa and alternative names include CAT or CHAT. The amyloid precursor protein (APP) is a transmembrane protein with a role in synaptic formation and repair and weighs approximately 100-140 kDa depending on its isoform. It is abundantly expressed in neurons. Dihydrofolate reductase (DHFR) is an important enzyme in folate metabolism vital for DNA synthesis and exists in many tissues especially in the liver. ENPP2 also known as autotaxin (ATX) is an enzyme involved in lysophospholipid metabolism with wide expression in various tissues.

Biological function summary

The synthesis of acetylcholine by ChAT is essential for cholinergic neurotransmission influencing muscle activation and several aspects of cognition. ChAT doesn't function as part of a complex acting independently to catalyze the conversion of acetyl-CoA and choline into acetylcholine. In contrast APP undergoes proteolytic processing leading to the formation of amyloid-beta associated with amyloid plaque formation in Alzheimer's disease. DHFR plays an integral role in the reduction of dihydrofolate to tetrahydrofolate critical for synthesizing nucleotides for DNA replication. ENPP2/ATX generates lysophosphatidic acid (LPA) which modulates cell proliferation and migration.

Pathways

ChAT is pivotal in the acetylcholine biosynthesis pathway interacting with other enzymes involved in neurotransmitter cycling such as acetylcholinesterase which breaks down acetylcholine. APP is central to the amyloidogenic and non-amyloidogenic pathways which include secretase-mediated cleavage that can also involve presenilin enzymes. DHFR is part of the folate pathway essential for the de novo synthesis of purine and thymidylate and shares involvement with the enzyme thymidylate synthase. ENPP2/ATX has significant roles in the LPA signaling pathway interacting with LPA receptors which activate various downstream signaling cascades.

Alterations in ChAT are associated with neurodegenerative diseases such as Alzheimer's where acetylcholine levels are critically reduced. In Alzheimer's disease APP through its cleavage products also plays an important pathogenic role associated with amyloid plaque formation. Meanwhile DHFR is a target in cancer treatment strategies where antifolate drugs aim to halt cancer cell proliferation by inhibiting folate metabolism. ENPP2/ATX links to several conditions including cancer metastasis and fibrosis related to its role in activating LPA signaling that influences cancer cell behavior.