Table 2 Summary of novel HPTMs in AD

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]