Interaction of amyloid beta with humanin and acetylcholinesterase is modulated by ATP.

Atali S, Dorandish S, Devos J, Williams A, Price D, Taylor J, Guthrie J, Heyl D, Evans HG

FEBS open bio18 Nov 2020Cited by 18 (Europe PMC)

PMID33145964PMCIDPMC7714071DOI10.1002/2211-5463.13023PepBankPUB-33145964

Summary

Humanin (HN) is known to bind amyloid beta (Aβ)-inducing cytoprotective effects, while binding of acetylcholinesterase (AChE) to Aβ increases its aggregation and cytotoxicity. Previously, we showed that binding of HN to Aβ blocks aggregation induced by AChE and that HN decreases but does not abolish Aβ-AChE interactions in A549 cell media. Here, we set out to shed light on factors that modulate the interactions of Aβ with HN and AChE. We found that binding of either HN or AChE to Aβ is not affected by heparan sulfate, while ATP, thought to reduce misfolding of Aβ, weakened interactions between AChE and Aβ but strengthened those between Aβ and HN. Using media from either A549 or H1299 lung cancer cells, we observed that more HN was bound to Aβ upon addition of ATP, while levels of AChE in a complex with Aβ were decreased by ATP addition to A549 cell media. Exogenous addition of ATP to either A549 or H1299 cell media increased interactions of endogenous HN with Aβ to a comparable extent despite differences in AChE expression in the two cell lines, and this was correlated with decreased binding of exogenously added HN to Aβ. Treatment with exogenous ATP had no effect on cell viability under all conditions examined. Exogenously added ATP did not affect viability of cells treated with AChE-immunodepleted media, and there was no apparent protection against the cytotoxicity resulting from immunodepletion of HN. Moreover, exogenously added ATP had no effect on the relative abundance of oligomer versus total Aβ in either cell line.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study6

3 results from studies that gave the peptide. No result from this study comes from people.

01LabIn vitro (cells)Mechanism
In A549 and H1299 cell media, the ATP-linked rise in endogenous humanin binding correlated with decreased binding of exogenously added humanin to amyloid beta.
In plain wordsIn lung cancer cell media, when ATP raised the cells' own humanin binding, added humanin bound amyloid beta less.
Peptide
Humanin
Outcome
DecreaseBinding of exogenous humanin to amyloid beta after ATP
Study
n: not reported in source
Media from A549 and H1299 lung cancer cells
Outcome group
Receptor activity and mechanism · Nervous system and cognition
Studied dose
Dose not stated
Source sentences
Summary
Exogenous addition of ATP to either A549 or H1299 cell media increased interactions of endogenous HN with Aβ to a comparable extent despite differences in AChE expression in the two cell lines, and this was correlated with decreased binding of exogenously added HN to Aβ.
Show in the study text Report a problemFND-3314596405
02LabIn vitro (cell-free)Mechanism
In binding assays, heparan sulfate did not affect the binding of humanin or acetylcholinesterase to amyloid beta.
In plain wordsIn lab tests, heparan sulfate did not change how humanin or AChE bound to amyloid beta.
Peptide
Humanin
Outcome
No significant changeHumanin binding to amyloid beta with heparan sulfate
Study
n: not reported in source
Binding assays of humanin, AChE and amyloid beta
Outcome group
Receptor activity and mechanism · Nervous system and cognition
Studied dose
Dose not stated
Source sentences
Summary
We found that binding of either HN or AChE to Aβ is not affected by heparan sulfate
Show in the study text Report a problemFND-3314596401
03LabIn vitro (cell-free)Mechanism
In binding assays, ATP strengthened the interaction between amyloid beta and humanin, while it weakened the interaction between AChE and amyloid beta.
In plain wordsIn lab tests, ATP made humanin bind amyloid beta more strongly, while it weakened AChE binding to amyloid beta.
Peptide
Humanin
Outcome
IncreaseHumanin binding to amyloid beta with ATP
Study
n: not reported in source
Binding assays of humanin, AChE and amyloid beta
Outcome group
Receptor activity and mechanism · Nervous system and cognition
Studied dose
Dose not stated
Source sentences
Summary
We found that binding of either HN or AChE to Aβ is not affected by heparan sulfate, while ATP, thought to reduce misfolding of Aβ, weakened interactions between AChE and Aβ but strengthened those between Aβ and HN
Show in the study text Report a problemFND-3314596402

Natural levels measured2

These results measure the body's own peptide. Nobody was given the peptide. They are not evidence about taking it. They are left out of key results, evidence counts and charts.

04LabEndogenous levelIn vitro (cells)Mechanism
In media from A549 or H1299 lung cancer cells, ATP addition increased the amount of the cells' own humanin bound to amyloid beta.
In plain wordsIn lung cancer cell media, adding ATP increased how much of the cells' own humanin was bound to amyloid beta.
Peptide
Humanin
Outcome
IncreaseHumanin bound to amyloid beta after ATP
Study
n: not reported in source
Media from A549 and H1299 lung cancer cells
Outcome group
Receptor activity and mechanism · Nervous system and cognition
Source sentences
Summary
Using media from either A549 or H1299 lung cancer cells, we observed that more HN was bound to Aβ upon addition of ATP, while levels of AChE in a complex with Aβ were decreased by ATP addition to A549 cell media.
This result measures the body's own Humanin. Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-3314596403
05LabEndogenous levelIn vitro (cells)Mechanism
ATP added to the media of A549 or H1299 cells increased interactions of endogenous humanin with amyloid beta to a comparable extent in both cell lines.
In plain wordsIn two lung cancer cell lines, ATP increased how much of the cells' own humanin interacted with amyloid beta, to a similar extent.
Peptide
Humanin
Outcome
IncreaseEndogenous humanin interaction with amyloid beta after ATP
Study
n: not reported in source
Media from A549 and H1299 lung cancer cells
Outcome group
Receptor activity and mechanism · Nervous system and cognition
Source sentences
Summary
Exogenous addition of ATP to either A549 or H1299 cell media increased interactions of endogenous HN with Aβ to a comparable extent despite differences in AChE expression in the two cell lines, and this was correlated with decreased binding of exogenously added HN to Aβ.
This result measures the body's own Humanin. Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-3314596404

Studies that did not test the peptide alone1

In this study, Humanin was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking Humanin.

06LabNot a test of Humanin aloneIn vitro (cells)Mechanism
In cells treated with AChE-immunodepleted media, exogenous ATP did not affect viability and gave no apparent protection against the cytotoxicity caused by immunodepletion of humanin.
In plain wordsIn lung cancer cell tests, ATP did not change cell survival and did not protect against harm caused by removing humanin.
Peptide
Humanin
Outcome
No significant changeCell viability after ATP with humanin immunodepletion
Study
n: not reported in source
A549 and H1299 cell media with AChE or humanin immunodepleted
Outcome group
Cell viability and death · Nervous system and cognition
Source sentences
Summary
Exogenously added ATP did not affect viability of cells treated with AChE-immunodepleted media, and there was no apparent protection against the cytotoxicity resulting from immunodepletion of HN.
In this study, Humanin was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Humanin.
Show in the study text Report a problemFND-3314596406

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
13 Oct 2026, 21:44 UTC
Study results updated
Version 1
13 Oct 2026, 16:31 UTC
First added · source update from Europe PMC

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