Photobiomodulation suppresses JNK3 by activation of ERK/MKP7 to attenuate AMPA receptor endocytosis in Alzheimer's disease.
Alzheimer's disease (AD), a severe age-related neurodegenerative disorder, lacks effective therapeutic methods at present. Physical approaches such as gamma frequency light flicker that can effectively reduce amyloid load have been reported recently. Our previous research showed that a physical method named photobiomodulation (PBM) therapy rescues Aβ-induced dendritic atrophy in vitro. However, it remains to be further investigated the mechanism by which PBM affects AD-related multiple pathological features to improve learning and memory deficits. Here, we found that PBM attenuated Aβ-induced synaptic dysfunction and neuronal death through MKP7-dependent suppression of JNK3, a brain-specific JNK isoform related to neurodegeneration. The results showed PBM-attenuated amyloid load, AMPA receptor endocytosis, dendrite injury, and inflammatory responses, thereby rescuing memory deficits in APP/PS1 mice. We noted JNK3 phosphorylation was dramatically decreased after PBM treatment in vivo and in vitro. Mechanistically, PBM activated ERK, which subsequently phosphorylated and stabilized MKP7, resulting in JNK3 inactivation. Furthermore, activation of ERK/MKP7 signaling by PBM increased the level of AMPA receptor subunit GluR 1 phosphorylation and attenuated AMPA receptor endocytosis in an AD pathological model. Collectively, these data demonstrated that PBM has potential therapeutic value in reducing multiple pathological features associated with AD, which is achieved by regulating JNK3, thus providing a noninvasive, and drug-free therapeutic strategy to impede AD progression.
['Shen|Qi|Q|', 'Liu|Lei|L|', 'Gu|Xiaotong|X|', 'Xing|Da|D|0000-0001-9752-8458']
D000544:Alzheimer Disease D000818:Animals D004195:Disease Models, Animal D004705:Endocytosis D006801:Humans D028022:Low-Level Light Therapy D008297:Male D051379:Mice D048057:Mitogen-Activated Protein Kinase 10 D018091:Receptors, AMPA
JNK3 AMPA receptor endocytosis Alzheimer's disease synaptic dysfunction Photobiomodulation therapy