Table 2.
Summary of novel HPTMs in AD
| Novel PTMs | Models | Sites | Gene/target pathways involved | Specific functions | References |
|---|---|---|---|---|---|
| Crotonylation | Wild-type and APPswe/PS1dE9 double transgenic mice (an AD mouse model), U251 cells transfected with the siNEAT1v2, siNEAT1(v1 + v2) or negative control siRNA | H3K27 | NEAT1, STAT3, CAV2, TGFB2, TGFBR1 | It can regulate endocytosis-related gene expression to inhibit the uptake of Aβ in AD | [61] |
| N2a/APP695swe cells | Pan-Kcr | – | – | [66] | |
| Lactylation | Brain tissue from AD mouse models, AD patients, BV2 cells | Pan-Kla; H4K18la; H4K5la; H4K8la; H3K18la; H3K23la | Glycolysis/H4K12la/PKM2 positive feedback loop | A glycolysis/H4K12la/PKM2 positive feedback loop that exacerbates microglial activation and dysfunction in AD | [67] |
| N2a/APP695swe cells, APP/PS1 Mice | Pan-Kla | – | Catalpol may play a neuroprotective role in AD by modulating lactylation | [68] | |
| β-hydroxybutyrylation | – | – | – | – | – |
| succinylation | Neurons from embryos were prepared from the cerebral cortices of E15.5 C57BL/6 mice | Pan-Ksucc | KGDHC | KGDHC can serve as a trans-succinylase that mediates succinylation in an α-ketoglutarate-dependent manner | [76] |
| Human brain tissue samples, transgenic mouse models of AD | Pan-Ksucc | – | Succinylation of APP disrupts its normal proteolytic processing, thereby promoting Aβ accumulation and plaque formation; in addition, succinylation of tau promotes its aggregation into tangles and impairs microtubule assembly | [4] | |
| Escherichia coli BL21/DE3 cells | Tau succinylation in residue K311 | – | K311 succinylation locally perturbs the binding of the tau MBD to tubulin | [80] | |
| N2a/APP695swe cells | Pan-Ksucc | – | – | 66] | |
| Malonylation | N2a/APP695swe cells | Pan-Kmal | – | – | [66] |
| 2-hydroxyisobutyrylation | N2a/APP695swe cells | Pan-Khib | – | – | [66] |
| N2a/APP695swe cells, APP/PS1 mice | Pan-Khib | – | – | [68] |