Achucarro Seminars

14 Jul [2017]

at 13.00 CET

Ciliary receptors modulate neuronal autophagy: impact of amyloid beta

Olatz Pampliega

Université de Bordeaux


Neurodegenerative diseases like Alzheimer's disease (AD) are characterized by the accumulation of neuropathogenic proteins that compromise autophagic function. In the search of new ways to upregulate autophagy with therapeutic purposes, we have previously described that signaling pathways clustered in the primary cilium (PC) activate autophagy. Neurons and glia in the CNS possess a PC that responds to neurotrophins, growth factors, hormones and other extracellular signaling elements, whereas neurons in the hippocampus require the PC for neuronal regeneration. Interestingly, it has been reported that Aβ binds selectively the p75NTR receptor, which localizes in the PC of hippocampal neurons. Moreover, AD animal models have a decreased PC length immunostained for p75NTR receptor. However, despite the increasing description of signaling pathways that require the PC for their effector mechanisms, the cellular mechanisms that govern these pathways are poorly understood in the adult brain. During my presentation I will show how p75NTR receptor signaling contributes to modulate autophagy, also during Aβ overload. In addition, our preliminary studies in vivo point to a differential effect of acute versus chronic Aβ accumulation over hippocampal PC, which could have differential effects over ciliary structure and functioning. Overall, these results will help characterizing ciliary signaling pathways that modulate autophagy in the hippocampus in physiological conditions as well as during Aβ pathology. In the long term, we could define through the PC new ways to burst autophagy for developing new therapeutic strategies against neurodegeneration.