Delta8-THC protects against amyloid beta toxicity modulating ER stress in vitro: a transcriptomic analysis

Alzheimer s disease (AD) represents the most common form of dementia, characterized by amyloid beta (Abeta) plaques and neurofibrillary tangles (NFTs). It is characterized by neuroinflammation, accumulation of misfolded protein, ER stress and apoptosis. It is of main importance to find new therapeutic strategies because its prevalence is increasing worldwide. Cannabinoids are promising neuroprotective phytocompounds and in particular non psychotropic ones are reaching attention. In this study we evaluated the neuroprotective potential of Delta8-THC pretreatment in an in vitro model of AD through transcriptomic analysis. We found that Delta8-THC pretreatment restored the loss of cell viability in retinoic acid-differentiated neuroblastoma SH-SY5Y cells treated with Abeta1-42. Moreover, transcriptomic analysis evidenced that enriched GO were related to ER functions and proteostasis. In particular, Abeta1-42 upregulated genes involved in ER stress and unfolded protein response, leading to apoptosis as demonstrated by the increase of Bax and decrease of Bcl-2 both at gene and protein expression levels. On the contrary, Delta8-THC pre-treatment reduced ER stress and as a consequence apoptosis. Then, the results demonstrated that Delta8-THC may represent a new neuroprotective agent in AD.