Aph1c is one of the genes encoding subunits of the gamma-secretase complex. Gamma-secretase is crucial for amyloid beta peptide release and is involved in Notch, N-Cadherin, and potentially other signaling pathways [1]. In rodents, it originated from a duplication of Aph1B [1].

In vivo studies using knockout mouse models have provided insights into Aph1c's function. Aph1C-/-mice can survive into adulthood [1]. However, combined Aph1BC-/-deficiency causes a mild but significant reduction in amyloid beta precursor protein processing in selective regions of the adult brain, suggesting that different gamma-secretase complexes containing Aph1c may have distinct biological functions [1]. Also, the Aph1B/C-gamma-secretase complex is expressed in brain areas relevant to schizophrenia pathogenesis, and Aph1BC(- / -) mice show accumulation of Nrg1 fragments in the brain, along with pharmacological and behavioral abnormalities that can be reversed by antipsychotic drugs [2].

In conclusion, Aph1c, as part of the gamma-secretase complex, is involved in important biological processes such as amyloid beta precursor protein processing and Nrg1 cleavage. The study of Aph1c using KO mouse models has revealed its potential role in diseases like Alzheimer's and schizophrenia, contributing to our understanding of the molecular mechanisms underlying these diseases and potentially guiding the development of more targeted therapies.

References:

1. Serneels, Lutgarde, Dejaegere, Tim, Craessaerts, Katleen, Hartmann, Dieter, De Strooper, Bart. 2005. Differential contribution of the three Aph1 genes to gamma-secretase activity in vivo. In Proceedings of the National Academy of Sciences of the United States of America, 102, 1719-24. doi:. https://pubmed.ncbi.nlm.nih.gov/15665098/

2. Dejaegere, T, Serneels, L, Schäfer, M K, D'Hooge, R, De Strooper, B. 2008. Deficiency of Aph1B/C-gamma-secretase disturbs Nrg1 cleavage and sensorimotor gating that can be reversed with antipsychotic treatment. In Proceedings of the National Academy of Sciences of the United States of America, 105, 9775-80. doi:10.1073/pnas.0800507105. https://pubmed.ncbi.nlm.nih.gov/18626010/