Table 1.

The correlation between the expression of PERK-dependent unfolded protein response (UPR)-related proteins and proteostasis disturbances in various neurodegenerative disorders. The upregulation of specific UPR markers in the listed experimental models is indicated as an up-arrow (↑), whereas downregulation as a down-arrow (↓).

Neurodegenerative Disease	UPR Markers	Experimental Model
Alzheimer’s disease	↑ GRP78	Aβ-treated SK-N-SH cells [203], RBE4 cells [204], Aβ1–40-treated RBE4 cells [205], Aβ1–42-treated bEnd.3 cells [206], 5XFAD mouse model [207], APP/PS1 transgenic mice [208], Aβ1–42-treated rat astrocytes, 3xTg-AD mice [209], mutant PS1 cells, 3xTg-AD mice [210].
	↓ GRP78	PS1 mutant SK-N-SH cells [211].
	↑ PERK	Hippocampus of human AD brains [48], 5XFAD mouse model [160,166], Aβ-treated SK-N-SH cells [203], JNPL3 mice, rat cortical neurons [212], Aβ42 transgenic flies [213], pR5 mice [214].
	↑ p-eIF2α	AD mouse model [215], hippocampus of human AD brains [48], 5XFAD mouse model [160,166], APP/PS1 mice [216], Aβ-treated SK-N-SH cells [203], JNPL3 mice, primary cultures of rat cortical neurons [212], Aβ1–42-treated rat embryonic hippocampal neurons [217], pR5 mice [214], Aβ1–42-treated rat primary cortical neurons [218], Aβ1–42-treated rat cerebral cortical astrocytes [209].
	↑ ATF4	5XFAD mouse model [160,166], Aβ1–40-treated RBE4 cells [205], human APOEe4 allele-expressing human and mouse AD models [219], Aβ1–42-treated rat embryonic hippocampal neurons, Aβ1–42-treated mice, human AD brains [217], Arg-61 APOE astrocytes [220].
	↑ CHOP	Aβ-treated SK-N-SH cells [203], primary rat cortical neurons [212], RBE4 cells [204], temporal cortex of human AD brains [221], Aβ1–40-treated RBE4 cell line [205], Aβ1–42-treated bEnd.3 cells [206], 5XFAD mouse model [207], APP/PS1 transgenic mice [208].
	↑ GADD34	J20 mice [222], AD mouse model, human AD brains [223].
Parkinson’s disease	↑ GRP78	SYN120 mice, SH-SY5Y+ cells, HEK 293 cells [95], PARK14 knock-in mouse model [224], 6-OHDA-treated MN9D cells [225], 6-OHDA-treated SH-SY5Y cells [226].
	↓ GRP78	Rat PD model [227,228], human PD brains [229], DJ-1 KO neurons, MEFs and KD SH-SY5Y+ cells [230].
	↑ PERK	Human PD brains, rat PD models [231], PARK20 fibroblasts [232], mouse model of chronic MPTP/P injection [233], rat PD model [228], PARK14 mice [224], 6-OHDA- or MPP+-treated MN9D cells [225], Drosophila PINK1 and PARKIN mutants [234], DJ-1 KO MEFs [230].
	↑ eIF2α	PARK20 fibroblasts [232], mouse model of chronic MPTP/P injection [233], 6-OHDA- or MPP+-treated MN9D cells [225], DJ-1 KO MEFs [230].
	↑ ATF4	Rat PD model [235], PD cellular models [95], mouse model of chronic MPTP/P injection [233], PARK20 fibroblasts [232].
	↓ ATF4	DJ-1 KO neurons, MEFs and KD SH-SY5Y+ cells [230].
	↑ CHOP	6-OHDA- or MPP+- treated MN9D cells [225], 6-OHDA-treated SH-SY5Y cells [226], PARK14 mice [224], rat PD model [228], PARK20 fibroblasts [232].
	↓ CHOP	DJ-1 KO neurons, MEFs and KD SH-SY5Y+ cells [230].
Huntington’s disease	↑ GRP78	PC6.3 cell [236], mHtt-expressing 293 Tet-Off cells [237], PC12-Q79 cells [238], HEK293T cells [239], Htt150Q-expressing N2a cells [240].
	↓ GRP78	mHtt-expressing mouse striatal cell lines [241].
	↑ PERK	Human and murine striatal cells, N171-82Q mice [242], PC12-Q79 cells [238].
	↑ eIF2α	Human and murine striatal cells, N171-82Q mice [242], 120Q-Htt-expressing PC6.3 cells [243].
	↑ ATF4	Q7 cells [244].
	↓ ATF4	Q111 cells [244].
	↑ CHOP	PC6.3 cell [236], PC12-Q79 cells [238], Q7 and Q111 cells [245], HEK293T cells [239].
Prion disease	↑ GRP78	PrP-expressing N2a cells [246], PrP(106-126)-treated NT2 rho0 cells and NT2 rho0+ cells [247], PrP-expressing N2a cells [248], 263K infected hamsters brain tissues, PrP-expressing 293-T cells [249], brains of BSE cattle [250], PrP-treated M17 cells [251].
	↓ GRP78	Prion infected GRP78+/− and GRP78+/+ mice, CAD5 cell line [106], CaBP-KO mice [252], PrP-treated CR7 cells [253].
	↑ PERK	Prion-infected mice [254], POM1-treated cultured organotypic cerebellar slices [255], FTgpi mice [256].
	↑ p-eIF2α	Prion-diseased mice [131,254], POM1-treated cultured organotypic cerebellar slices [255], FTgpi mice [256].
	↑ ATF4	POM1-treated cultured organotypic cerebellar slices [255].
	↑ CHOP	FTgpi mice [256], PrP-expressing N2a cells [246], CaBP-KO mice [252], PrP-treated SH-SY5Y cells [257].