670 nm Laser Light and EGCG Complementarily Reduce Amyloid-β Aggregates in Human Neuroblastoma Cells: Basis for Treatment of Alzheimer's Disease?

Abstract

Objective: The aim of the present study is to present the results of in vitro experiments with possible relevance in the treatment of Alzheimer's disease (AD). Background Data: Despite intensive research efforts, there is no treatment for AD. One root cause of AD is the extra-and intracellular deposition of amyloid-beta (Ab) fibrils in the brain. Recently, it was shown that extracellular Ab can enter brain cells, resulting in neurotoxicity. Methods: After internalization of Ab 42 into human neuroblastoma (SH-EP) cells, they were irradiated with moderately intense 670-nm laser light (1000 Wm -2 ) and/or treated with epigallocatechin gallate (EGCG). Results: In irradiated cells, Ab 42 aggregate amounts were significantly lower than in nonirradiated cells. Likewise, in EGCGtreated cells, Ab 42 aggregate amounts were significantly lower than in non-EGCG-treated cells. Except for the cells simultaneously laden with Ab 42 and EGCG, there was a significant increase in cell numbers in response to laser irradiation. EGCG alone had no effect on cell proliferation. Laser irradiation significantly increased ATP levels in Ab 42 -free cells, when compared to nonirradiated cells. Laser-induced clearance of Ab 42 aggregates occurred at the expense of cellular ATP. Conclusions: Irradiation with moderate levels of 670-nm light and EGCG supplementation complementarily reduces Ab aggregates in SH-EP cells. Transcranial penetration of moderate levels of red to near-infrared (NIR) light has already been amply exploited in the treatment of patients with acute stroke; the blood-brain barrier (BBB) penetration of EGCG has been demonstrated in animals. We hope that our approach will inspire a practical therapy for AD.

Transcranial Low-Level Laser Therapy for Depression and Alzheimer’s Disease

“…LLLT has a prosurvival effect on Aβ-induced apoptosis and may be an effective therapeutic strategy in treating AD by targeting GSK3b [17]. In addition, another study on EGCG has also found that irradiation with moderate levels of 670-nm light and EGCG supplementation complementarily reduces Aβ aggregation in human neuroblastoma SH-EP cells [18]. Further, Zhang et al has uncovered evidence that LLLT could inhibit Aβ 25-35-induced cell apoptosis through activation of Akt/Yesassociated protein (YAP)/p73 signaling pathway [19].…”

“…Extracellular accumulation of amyloid β (Aβ) peptide aggregates, which results in the formation of senile plaques, indicates one of the neuropathological markers of AD [39]. In recent years, accumulating evidence has suggested that transcranial LLLT suppresses Aβ-induced hippocampal neurodegeneration Increased the nuclear translocation of -catenin and enhanced its T cell factor/ lymphocyte enhancer factor-dependent transcriptional activity [17,18] hippocampus were significantly down-regulated in Ahi1 KO mice, which reveals depressive-like behaviors [4]. Transcranial LLLT attenuated depressive-like behaviors in Ahi1 KO mice, which could be involved in the enhancement of serotonin and dopamine levels in the brain [4].…”

“…Recently, researchers have shifted the focus of research to the application of LLLT on brain disorders [1][2][3]. During the past decade, LLLT has been widely used to study neurological and psychological diseases [3] such as depressionlike behaviors [4][5][6][7][8], Alzheimer's disease (AD) [9][10][11][12][13][14][15][16][17][18][19][20], Parkinson's disease [21], stroke [22,23] and traumatic brain injury (TBI) [24][25][26][27][28][29][30][31][32]. Because red or NIR light can effectively penetrate into brain tissues [33,34], it can be noninvasive and play a beneficial role in increasing ATP biosynthesis and neurogenesis [1,2].…”

“…Moreover, LLLT also inhibited Aβ 25-35-induced pheochromocytoma (PC12) cell apoptosis [20]. Furthermore, laser irradiation with moderate levels of 670-nm light and epigallocatechin gallate (EGCG) supplementation complementarily decreased Aβ aggregates in human neuroblastoma (SH-EP) cells [18]. More detailed information was summarized in Table 2.…”

Natural Compounds May Open New Routes to Treatment of Amyloid Diseases

“…It can stimulate mitochondrial metabolism [121] and enhance the effectiveness of EGCG in preventing the proliferation of tumor cells [120]. The combination of pulsed laser irradiation at 670 nm with the intake of EGCG decreased the amount of Aβ aggregates and improves the metabolic activity in a neuroblastoma cell model [122].…”