Urolithin A improves Alzheimer's disease cognition and restores mitophagy and lysosomal functions

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Urolithin A improves Alzheimer's disease cognition and restores mitophagy and lysosomal functions. / Hou, Yujun; Chu, Xixia; Park, Jae Hyeon; Zhu, Qing; Hussain, Mansoor; Li, Zhiquan; Madsen, Helena Borland; Yang, Beimeng; Wei, Yong; Wang, Yue; Fang, Evandro F.; Croteau, Deborah L.; Bohr, Vilhelm A.

In: Alzheimer's and Dementia, Vol. 20, No. 6, 2024, p. 4212-4233.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Hou, Y, Chu, X, Park, JH, Zhu, Q, Hussain, M, Li, Z, Madsen, HB, Yang, B, Wei, Y, Wang, Y, Fang, EF, Croteau, DL & Bohr, VA 2024, 'Urolithin A improves Alzheimer's disease cognition and restores mitophagy and lysosomal functions', Alzheimer's and Dementia, vol. 20, no. 6, pp. 4212-4233. https://doi.org/10.1002/alz.13847

APA

Hou, Y., Chu, X., Park, J. H., Zhu, Q., Hussain, M., Li, Z., Madsen, H. B., Yang, B., Wei, Y., Wang, Y., Fang, E. F., Croteau, D. L., & Bohr, V. A. (2024). Urolithin A improves Alzheimer's disease cognition and restores mitophagy and lysosomal functions. Alzheimer's and Dementia, 20(6), 4212-4233. https://doi.org/10.1002/alz.13847

Vancouver

Hou Y, Chu X, Park JH, Zhu Q, Hussain M, Li Z et al. Urolithin A improves Alzheimer's disease cognition and restores mitophagy and lysosomal functions. Alzheimer's and Dementia. 2024;20(6):4212-4233. https://doi.org/10.1002/alz.13847

Author

Hou, Yujun ; Chu, Xixia ; Park, Jae Hyeon ; Zhu, Qing ; Hussain, Mansoor ; Li, Zhiquan ; Madsen, Helena Borland ; Yang, Beimeng ; Wei, Yong ; Wang, Yue ; Fang, Evandro F. ; Croteau, Deborah L. ; Bohr, Vilhelm A. / Urolithin A improves Alzheimer's disease cognition and restores mitophagy and lysosomal functions. In: Alzheimer's and Dementia. 2024 ; Vol. 20, No. 6. pp. 4212-4233.

Bibtex

@article{8532ee1b0a3f42c19c00ab483fda5b2e,
title = "Urolithin A improves Alzheimer's disease cognition and restores mitophagy and lysosomal functions",
abstract = "BACKGROUND: Compromised autophagy, including impaired mitophagy and lysosomal function, plays pivotal roles in Alzheimer's disease (AD). Urolithin A (UA) is a gut microbial metabolite of ellagic acid that stimulates mitophagy. The effects of UA's long-term treatment of AD and mechanisms of action are unknown. METHODS: We addressed these questions in three mouse models of AD with behavioral, electrophysiological, biochemical, and bioinformatic approaches. RESULTS: Long-term UA treatment significantly improved learning, memory, and olfactory function in different AD transgenic mice. UA also reduced amyloid beta (Aβ) and tau pathologies and enhanced long-term potentiation. UA induced mitophagy via increasing lysosomal functions. UA improved cellular lysosomal function and normalized lysosomal cathepsins, primarily cathepsin Z, to restore lysosomal function in AD, indicating the critical role of cathepsins in UA-induced therapeutic effects on AD. CONCLUSIONS: Our study highlights the importance of lysosomal dysfunction in AD etiology and points to the high translational potential of UA. Highlights: Long-term urolithin A (UA) treatment improved learning, memory, and olfactory function in Alzheimer's disease (AD) mice. UA restored lysosomal functions in part by regulating cathepsin Z (Ctsz) protein. UA modulates immune responses and AD-specific pathophysiological pathways.",
keywords = "Alzheimer's disease, autophagy, cathepsin Z, DNA repair, lysosome, mitophagy, neuroinflammation, urolithin A",
author = "Yujun Hou and Xixia Chu and Park, {Jae Hyeon} and Qing Zhu and Mansoor Hussain and Zhiquan Li and Madsen, {Helena Borland} and Beimeng Yang and Yong Wei and Yue Wang and Fang, {Evandro F.} and Croteau, {Deborah L.} and Bohr, {Vilhelm A.}",
note = "Publisher Copyright: {\textcopyright} 2024 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.",
year = "2024",
doi = "10.1002/alz.13847",
language = "English",
volume = "20",
pages = "4212--4233",
journal = "Alzheimer's & Dementia",
issn = "1552-5260",
publisher = "Elsevier",
number = "6",

}

RIS

TY - JOUR

T1 - Urolithin A improves Alzheimer's disease cognition and restores mitophagy and lysosomal functions

AU - Hou, Yujun

AU - Chu, Xixia

AU - Park, Jae Hyeon

AU - Zhu, Qing

AU - Hussain, Mansoor

AU - Li, Zhiquan

AU - Madsen, Helena Borland

AU - Yang, Beimeng

AU - Wei, Yong

AU - Wang, Yue

AU - Fang, Evandro F.

AU - Croteau, Deborah L.

AU - Bohr, Vilhelm A.

N1 - Publisher Copyright: © 2024 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.

PY - 2024

Y1 - 2024

N2 - BACKGROUND: Compromised autophagy, including impaired mitophagy and lysosomal function, plays pivotal roles in Alzheimer's disease (AD). Urolithin A (UA) is a gut microbial metabolite of ellagic acid that stimulates mitophagy. The effects of UA's long-term treatment of AD and mechanisms of action are unknown. METHODS: We addressed these questions in three mouse models of AD with behavioral, electrophysiological, biochemical, and bioinformatic approaches. RESULTS: Long-term UA treatment significantly improved learning, memory, and olfactory function in different AD transgenic mice. UA also reduced amyloid beta (Aβ) and tau pathologies and enhanced long-term potentiation. UA induced mitophagy via increasing lysosomal functions. UA improved cellular lysosomal function and normalized lysosomal cathepsins, primarily cathepsin Z, to restore lysosomal function in AD, indicating the critical role of cathepsins in UA-induced therapeutic effects on AD. CONCLUSIONS: Our study highlights the importance of lysosomal dysfunction in AD etiology and points to the high translational potential of UA. Highlights: Long-term urolithin A (UA) treatment improved learning, memory, and olfactory function in Alzheimer's disease (AD) mice. UA restored lysosomal functions in part by regulating cathepsin Z (Ctsz) protein. UA modulates immune responses and AD-specific pathophysiological pathways.

AB - BACKGROUND: Compromised autophagy, including impaired mitophagy and lysosomal function, plays pivotal roles in Alzheimer's disease (AD). Urolithin A (UA) is a gut microbial metabolite of ellagic acid that stimulates mitophagy. The effects of UA's long-term treatment of AD and mechanisms of action are unknown. METHODS: We addressed these questions in three mouse models of AD with behavioral, electrophysiological, biochemical, and bioinformatic approaches. RESULTS: Long-term UA treatment significantly improved learning, memory, and olfactory function in different AD transgenic mice. UA also reduced amyloid beta (Aβ) and tau pathologies and enhanced long-term potentiation. UA induced mitophagy via increasing lysosomal functions. UA improved cellular lysosomal function and normalized lysosomal cathepsins, primarily cathepsin Z, to restore lysosomal function in AD, indicating the critical role of cathepsins in UA-induced therapeutic effects on AD. CONCLUSIONS: Our study highlights the importance of lysosomal dysfunction in AD etiology and points to the high translational potential of UA. Highlights: Long-term urolithin A (UA) treatment improved learning, memory, and olfactory function in Alzheimer's disease (AD) mice. UA restored lysosomal functions in part by regulating cathepsin Z (Ctsz) protein. UA modulates immune responses and AD-specific pathophysiological pathways.

KW - Alzheimer's disease

KW - autophagy

KW - cathepsin Z

KW - DNA repair

KW - lysosome

KW - mitophagy

KW - neuroinflammation

KW - urolithin A

U2 - 10.1002/alz.13847

DO - 10.1002/alz.13847

M3 - Journal article

C2 - 38753870

AN - SCOPUS:85193251961

VL - 20

SP - 4212

EP - 4233

JO - Alzheimer's & Dementia

JF - Alzheimer's & Dementia

SN - 1552-5260

IS - 6

ER -

ID: 392876048