Differential effect of amyloid beta peptides on mitochondrial axonal trafficking depends on their state of aggregation and binding to the plasma membrane.

Neurobiology of Disease
Liang ZhangEugenia Trushina

Abstract

Inhibition of mitochondrial axonal trafficking by amyloid beta (Aβ) peptides has been implicated in early pathophysiology of Alzheimer's Disease (AD). Yet, it remains unclear whether the loss of motility inevitably induces the loss of mitochondrial function, and whether restoration of axonal trafficking represents a valid therapeutic target. Moreover, while some investigations identify Aβ oligomers as the culprit of trafficking inhibition, others propose that fibrils play the detrimental role. We have examined the effect of a panel of Aβ peptides with different mutations found in familial AD on mitochondrial motility in primary cortical mouse neurons. Peptides with higher propensity to aggregate inhibit mitochondrial trafficking to a greater extent with fibrils inducing the strongest inhibition. Binding of Aβ peptides to the plasma membrane was sufficient to induce trafficking inhibition where peptides with reduced plasma membrane binding and internalization had lesser effect on mitochondrial motility. We also found that Aβ peptide with Icelandic mutation A673T affects axonal trafficking of mitochondria but has very low rates of plasma membrane binding and internalization in neurons, which could explain its relatively low toxic...Continue Reading

Citations

Oct 20, 2018·Molecular Neurobiology·Athanasios AlexiouGhulam Md Ashraf
Nov 5, 2019·Proceedings of the National Academy of Sciences of the United States of America·Manish SharmaSrinivasa Subramaniam
Jan 26, 2020·The FEBS Journal·Senthilkumar SivanesanJayakumar Rajadas
Sep 25, 2018·Journal of Alzheimer's Disease : JAD·Tim L EmmerzaalTamas Kozicz
Oct 8, 2020·Journal of Neurochemistry·Colleen S LimegroverSusan M Catalano
Nov 17, 2020·Frontiers in Aging Neuroscience·Natalia SalvadoresFelipe A Court
Mar 26, 2021·Frontiers in Aging Neuroscience·Biyao WangXinwen Zhang
May 8, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Karolina DrabikJoanna Szczepanowska
Jul 3, 2021·International Journal of Molecular Sciences·Miriam SciaccalugaCinzia Costa

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Methods Mentioned

BETA
transgenic
PCR
atomic
electron microscopy
AFM
dynamic light scattering
atomic force microscopy
confocal microscopy
acetylation

Software Mentioned

NanoScope
TMRM
LSM 510

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