Aβ42 oligomers selectively disrupt neuronal calcium release

Lazzari, Cristian; Kipanyula, Maulilio J.; Agostini, Mario; Pozzan, Tullio; Fasolato, Cristina

doi:10.1016/j.neurobiolaging.2014.10.020

Cited by 45 publications

(33 citation statements)

References 69 publications

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“…We tested the effect on Tau of either oligomers or monomers of Ab1-42. Ab oligomers lower neuronal activity, through various mechanisms (Bero et al, 2011;Brouillette et al, 2012;Pitt et al, 2013;Tu et al, 2014;Xu et al, 2014;Lazzari et al, 2015). Instead, Ab monomers enhance various cellular functions (Giuffrida et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

Beta‐amyloid 1‐42 monomers, but not oligomers, produce PHF ‐like conformation of Tau protein

et al. 2016

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SummaryThe mechanistic relationship between amyloid β1‐42 (Aβ1‐42) and the alteration of Tau protein are debated. We investigated the effect of Aβ1‐42 monomers and oligomers on Tau, using mice expressing wild‐type human Tau that do not spontaneously develop Tau pathology. After intraventricular injection of Aβ1‐42, mice were sacrificed after 3 h or 4 days. The short‐lasting treatment with Aβ monomers, but not oligomers, showed a conformational PHF‐like change of Tau, together with hyperphosphorylation. The same treatment induced increase in concentration of GSK3 and MAP kinases. The inhibition of the kinases rescued the Tau changes. Aβ monomers increased the levels of total Tau, through the inhibition of proteasomal degradation. Aβ oligomers reproduced all the aforementioned alterations only after 4 days of treatment. It is known that Aβ1‐42 monomers foster synaptic activity. Our results suggest that Aβ monomers physiologically favor Tau activity and dendritic sprouting, whereas their excess causes Tau pathology. Moreover, our study indicates that anti‐Aβ therapies should be targeted to Aβ1‐42 monomers too.

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Section: Discussionmentioning

confidence: 99%

Beta‐amyloid 1‐42 monomers, but not oligomers, produce PHF ‐like conformation of Tau protein

et al. 2016

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“…The synaptic action of Aβ triggers aberrant activation of NMDARs (Wu and Hou ), Ca 2+ deregulation (Lazzari et al . ), and cellular stress, which in turn leads to synaptic dysfunction and neuronal loss (reviewed in Ferreira et al . ).…”

Section: Synapses and Neurodegenerative Diseasesmentioning

confidence: 99%

“…The precise mechanisms of Ab toxicity are not fully understood, but it is believed that oligomers can interact with a number of synaptic proteins including mGluRs and iGluRs (De Felice et al 2007;Renner et al 2010;Um et al 2013), a7-nicotinic acetylcholine receptors (Wang et al 2000), p75 neurotrophin receptor (Yaar et al 1997;Sotthibundhu et al 2008), NLGN-1 (Dinamarca et al 2011), cellular prion protein (Lauren et al 2009), and PSD95 (Pham et al 2010). The synaptic action of Ab triggers aberrant activation of NMDARs (Wu and Hou 2010), Ca 2+ deregulation (Lazzari et al 2015), and cellular stress, which in turn leads to synaptic dysfunction and neuronal loss (reviewed in Ferreira et al 2015). Soluble Ab further exacerbates neurotransmitter release at excitatory synapses, including glutamate and the NMDAR co-agonist D-serine, thereby triggering postsynaptic neurotoxicity and synapse failure (Paula-Lima et al 2013;Talantova et al 2013;Madeira et al 2015).…”

Section: Synapses and Neurodegenerative Diseasesmentioning

confidence: 99%

Synaptopathies: synaptic dysfunction in neurological disorders – A review from students to students

Lepeta

Lourenco

Schweitzer

et al. 2016

Journal of Neurochemistry

296

220

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Synapses are essential components of neurons and allow information to travel coordinately throughout the nervous system to adjust behavior to environmental stimuli and to control body functions, memories, and emotions. Thus, optimal synaptic communication is required for proper brain physiology, and slight perturbations of synapse function can lead to brain disorders. In fact, increasing evidence has demonstrated the relevance of synapse dysfunction as a major determinant of many neurological diseases. This notion has led to the concept of synaptopathies as brain diseases with synapse defects as shared pathogenic features. In this review, which was initiated at the 13th International Society for Neurochemistry Advanced School, we discuss basic concepts of synapse structure and function, and provide a critical view of how aberrant synapse physiology may contribute to neurodevelopmental disorders (autism, Down syndrome, startle disease, and epilepsy) as well as neurodegenerative disorders (Alzheimer and Parkinson disease). We finally discuss the appropriateness and potential implications of gathering synapse diseases under a single term. Understanding common causes and intrinsic differences in diseaseassociated synaptic dysfunction could offer novel clues toward synapse-based therapeutic intervention for neurological and neuropsychiatric disorders.

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“…Double labeled elements are rarely seen in the field. Scale bar = 50 m (Roselli et al, 2005;Wei et al, 2008;Q24 Demuro and Parker, 403 2013; Atherton et al, 2014;Lazzari et al, 2014). On the other side, 404 calcium stress and calpain/caspase activation may act as an upstream 405 factor to induce β-amyloid overproduction (Liang et al, 2010).…”

mentioning

confidence: 99%

Age-related intraneuronal accumulation of αII-spectrin breakdown product SBDP120 in the human cerebrum is enhanced in Alzheimer's disease

Zhu

Xue

Qiu

et al. 2015

Experimental Gerontology

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Aβ42 oligomers selectively disrupt neuronal calcium release

Cited by 45 publications

References 69 publications

Beta‐amyloid 1‐42 monomers, but not oligomers, produce PHF ‐like conformation of Tau protein

Beta‐amyloid 1‐42 monomers, but not oligomers, produce PHF ‐like conformation of Tau protein

Synaptopathies: synaptic dysfunction in neurological disorders – A review from students to students

Age-related intraneuronal accumulation of αII-spectrin breakdown product SBDP120 in the human cerebrum is enhanced in Alzheimer's disease

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