TCDB is operated by the Saier Lab Bioinformatics Group
TCIDNameDomainKingdom/PhylumProtein(s)
1.C.50.1.1









Alzheimer''s disease amyloid β-protein (amino acids 1-42) (Abeta protein or AβP or Aβ42).  Aβ pores may consist of tetrameric and hexameric beta-sheet subunits (Strodel et al. 2010).  Residues 22 - 35 in the peptide binds cholesterol to form Ca2+-permeable pores (Di Scala et al. 2014).  Cholesterol promotes the insertion of Abeta in the plasma membrane, induces alpha-helical structure formation, and forces the peptide to adopt a tilted topology that favours oligomerization. Bexarotene, an amphipathic drug for the treatment of neurodegenerative diseases, competes with cholesterol for binding to Abeta and prevents oligomeric channel formation (Di Scala et al. 2014). The beta-amyloid protein is involved in the activation of the nAChRalpha7 receptor (Hassan et al. 2019). Tryptophan enantiomers (d/l-Trp) introduced into artificial nanochannels regulate the chiral selective transport of Abeta proteins; the l-Trp channel shows selectivity for the transport of Abeta protein (Zhu et al. 2020). The prevalence, presentation, and progression of Alzheimer's disease (AD) differ between men and women, although β-amyloid (Aβ) deposition is a pathological hallmark of AD in both sexes. Aβ-induced activation of the neuronal glutamate receptor mGluR5 is linked to AD progression. However, mGluR5 exhibits distinct sex-dependent profiles (Abd-Elrahman et al. 2020). mGluR5 isolated from male mouse cortical and hippocampal tissues bound with high affinity to Aβ oligomers, whereas mGluR5 from female mice exhibited no such affinity. This sex-selective Aβ-mGluR5 interaction is not depend on estrogen, but rather Aβ interaction with cellular prion protein (PrPC), which was detected only in male mouse brain homogenates. The ternary complex between mGluR5, Aβ oligomers, and PrPC was essential to elicit mGluR5-dependent pathological suppression of autophagy in primary neuronal cultures. Pharmacological inhibition of mGluR5 reactivated autophagy, mitigated Aβ pathology, and reversed cognitive decline in male APPswe/PS1ΔE9 mice, but not in their female counterparts. Aβ oligomers also bound with high affinity to human mGluR5 isolated from postmortem donor male cortical brain tissue, but not that from female samples, suggesting that this mechanism may be relevant to patients. mGluR5 does not contribute to Aβ pathology in females, highlighting the complexity of mGluR5 pharmacology and Aβ signaling that supports the need for sex-specific stratification in clinical trials assessing AD therapeutics (Abd-Elrahman et al. 2020). Proteins associated with or anchored to the plasma membrane are associated with cerebrospinal fluid biomarkers of amyloid and tau pathology in AD (Remnestål et al. 2021). The architecture of the Alzheimer's A beta P ion channel pore has been determined (Arispe 2004). A transmembrane annular polymeric structure may be responsible for the ion channel properties of the membrane-bound A beta P (Arispe 2004). Arispe 2004 synthesized peptides that encompass the histidine dyad (H-H) hypothesized to line the pore and showed that peptides designed to most closely match the proposed pore are the most effecAbd-Elrahman et al. 2020). mGluR5 isolated from male mouse cortical and hippocampal tissues bound with high affinity to Aβ oligomers, whereas mGluR5 from female mice exhibited no such affinity. This sex-selective Aβ-mGluR5 interaction is not depend on estrogen, but rather Aβ interaction with cellular prion protein (PrPC), which was detected only in male mouse brain homogenates. The ternary complex between mGluR5, Aβ oligomers, and PrPC was essential to elicit mGluR5-dependent pathological suppression of autophagy in primary neuronal cultures. Pharmacological inhibition of mGluR5 reactivated autophagy, mitigated Aβ pathology, and reversed cognitive decline in male APPswe/PS1ΔE9 mice, but not in their female counterparts. Aβ oligomers also bound with high affinity to human mGluR5 isolated from postmortem donor male cortical brain tissue, but not that from female samples, suggesting that this mechanism may be relevant to patients. mGluR5 does not contribute to Aβ pathology in females, highlighting the complexity of mGluR5 pharmacology and Aβ signaling that supports the need for sex-specific stratification in clinical trials assessing AD therapeutics (Abd-Elrahman et al. 2020). Proteins associated with or anchored to the plasma membrane are associated with cerebrospinal fluid biomarkers of amyloid and tau pathology in AD (Remnestål et al. 2021). The architecture of the Alzheimer's A beta P ion channel pore has been determined (Arispe 2004). A transmembrane annular polymeric structure may be responsible for the ion channel properties of the membrane-bound A beta P (Arispe 2004). Arispe 2004 synthesized peptides that encompass the histidine dyad (H-H) hypothesized to line the pore and showed that peptides designed to most closely match the proposed pore are the most effective at blocking ion currents through the membrane-incorporated A beta P channel.

Eukaryota
Metazoa
AβP of Rattus norvegicus
1.C.50.1.2









The Alzheimer’s disease amyloid β-protein (Aβpeptide; precursor: App, γ-secretase) (42aas) (3-d structure is known from NMR spectroscopy (1Z0Q_A; Jang et al., 2007; Zheng et al., 2008)).  This peptide is derived from the amyloid βA4 protein isoform f (NP_001129602)) which forms variable oligomeric toxic pores leading to cytosolic calcium elevation and Alzheimer's disease (Demuro et al., 2011). The monomer of Ass1-42 normally activates type-1 insulin-like growth factor receptors and enhances glucose uptake in neurons and peripheral cells by promoting the translocation of the Glut3 glucose transporter from the cytosol to the plasma membrane (Giuffrida et al. 2015). At nanomolar concentrations, APPsα is an allosteric activator of α7-nAcChR (see TC family 1.A.9), mediated by the C-terminal 16 aas (CTα16) (Korte 2019).

Eukaryota
Metazoa
Aβ-peptide from the amyloid βA4 protein isoform f of Homo sapiens (NP_001129602)
1.C.50.1.3









Beta amyloid protein-like, isoform D of 888 aas

Eukaryota
Metazoa

Beta amyloid protein-like, isoform D  of Drosophila melanogaster
1.C.50.1.4









Amyloid protein 1 of 629 aas

Eukaryota
Metazoa
Amyloid protein 1 of Hydra vulgaris (Hydra) (Hydra attenuata)