Table 1.

Effects of celastrol in Alzheimer’s disease, Parkinson’s disease, and Amiotrophyc lateral sclerosis.

Neurodegenerative Disease	In Vitro/In Vivo	Celastrol Effects	Doses/IC50	References
Alzheimer’s disease	In vitro - Human monocytes and macrophages - endothelial cells	- Suppression of IL-1βproduction	30 nM	[31]
		- Suppression of TNF-α production	70 nM
		- Decrease of the production of induced but not constitutive nitric oxide	50 nM IC50 = 100 nM
	In vivo - LPS rat model	- Improvement of memory, learning and performance in psychomotor activity tests	7 µg/kg i.p.
	In vitro - Stable NF-κB luciferase reporter cell line of HEK293 cells - 7 W CHO cells overexpressing wild-type human APP	- Prevention of NF-κB activation	IC50 < 1 μM	[32]
		- Inhibition of BACE-1 expression	5 μM
	In vivo - Transgenic mice overexpressing the human APP695sw mutation and the presenilin-1 mutation M146L (Tg PS1/APPsw)	- Reduction of APP beta-cleavage with consequently inhibition of Aß1–40 and Aß1–42 production- Decrease of both soluble and insoluble Aß1–38, Aß1–40 and Aß1–42 levels - Reduction of Aß plaque burden -Microglia activation	2.5 mg/kg/day s.c. long-lasting
	In vitro - H4 human neuroglioma cells transfected to overexpress human full length APP	- Reduction of Aß production induced by LPS - Increase of Hsp70 and Bcl-2 expression - Decrease of NF-κB activity - Induction of GSK-3β posphorylation at tyrosine 216 - Reduction of COX2 expression - Decrease of Aß accumulation	1, 10, and 100 nM (dose-dependently)	[33]
	In vitro - SH-SY5Y cells treated with Aβ1-42	- Inhibition of Tau hyperphosphorylation and Hsp90 expression, induced by Aβ1–42 - No effects on the decreased HSP70 and HSF-1 expression, Tau ubiquitination, and HSP70/Tau- HSP70/CHIP interaction induced by Aβ1–42	600 nmol/L	[34]
Parkinson’s disease	In vitro - Mouse primary cortical neurons and neuroblastoma SH-SY5Y cells incubated with lactacystin	- Absence of neuroprotective effects under conditions of the ubiquitin-proteasome system inhibition	1 µM (co-treatment) 0.01 an 0.1 µM (pre-treatment)	[35]
		- Reduction of cell viability and enhancement of cell death at high concentrations	1 and 2.5 µM
	In vivo - Lactacystin rat model	- No effects on the decrease of levels of dopamine and its metabolites - Absence of neuroprotective effects on dopaminergic neurons of the substantia nigra	0.3, 1 or 3 mg/kg/1 mL i.p.
		- Potentiation of the decrease in the levels of dopamine and its metabolites in the lesioned striatum - Acceleration of the total dopamine metabolism - Enhanced oxidative stress - Decrease in the number and/or density of dopaminergic neurons in the substantia nigra	3 mg/kg/1 mL i.p.
	In vitro - Human dopaminergic neuronal cell line (SH-SY5Y) treated with rotenone	- Protection from cell-injury induced and death induced by rotenone - Prevention of free radical production - Prevention of mitochondria membrane potential - Inhibition of cytochrome c release - Inhibition of Bax/Bcl-2 changes - Inhibition of caspase-9/3 activation - Inhibition of the activation of the p38 mitogen-activated protein kinase	2.5 nM	[36]
	In vivo - MPTP-treated mice	- Attenuation (48%) of the loss of dopaminergic neurons of the substantia nigra - Reduction of dopamine concentration depletion - Induction of Hsp70 expression in dopaminergic neurons - Decrease of TNF-α and NF-κB immunostaining - Reduction of astrogliosis	3 mg/kg i.p.	[25]
	In vivo - Drosophila DJ-1A model	- Neuroprotective effects on dopaminergic neurons	5 and 20 µg	[37]
	In vitro - Dopaminergic neuronal cell line (SH-SY5Y) treated with treated with MPP+	- Reduction of the MPP+-induced dopaminergic neuronal death, mitochondrial membrane depolarization, and ATP reduction	0.1–3 μM celastrol (dose dependently)	[38]
	In vivo - MPTP-treated mice	- Suppression of motor symptoms and neurodegeneration in the substantia nigra and striatum - Enhancement of mitophagy in the striatum	3 mg/kg/day i.p. for 3 days
Amyotrophic lateral sclerosis	In vitro -SOD1G93A transfected NSC34 cells	- Attenuation of H2O2-induced cell death - Decrease of MDA levels -Enhanced GCLC and GST mRNA expressions -Induction of ERK1/2 and Akt	50 nmol/L	[39]
	In vitro - Primary motoneuron cultures treated with staurosporin or H2O2	- Induction of Hsp70 - Absence of neuroprotective effects - Neurotoxic effects and induction of cell death - Induction of the apoptotic cell death cascade	0.3 and 3 μM	[40]
	In vitro - Differentiated neurons	- Neuroprotective effects via induced Hsp70 expression	0.75 μM	[24,41]
	In vivo - G93A SOD1 transgenic mouse model		2 mg/kg and 8 mg/kg p.o.
	In vivo - G93A SOD1 transgenic mouse model	- Improvement of weight loss and motor performance - Delay of the onset of the disease - Increase (30%) in the neuronal number in the lumbar spinal cord - Decrease of TNF-α, iNOS, CD40, and GFAP immunoreactivity in the lumbar spinal cord - Increase of Hsp70 immunoreactivity in lumbar spinal cord neurons	2 mg/kg and 8 mg/kg p.o.	[27]
Huntington’s disease	In vivo 3-nitropropionic acid rat model	- Decrease of the lesion volume in the striatum	3 mg/kg i.p.	[25]
	In vitro - Cell lines expressing mutant polyglutamine protein	- Reduction of the cell killing	0.4, 0.8 and 1.6 μM	[42]
	In vitro - Striatal cell line from the HdhQ111/Q111 knock-in mouse	- Inhibition of mutant huntingtin aggregation - Reverse of the abnormal cellular localization of full-length mutant huntingtin in mutant HdhQ111/Q111 striatal cells	0.25 μM	[26]