Klotho an Autophagy Stimulator as a Potential Therapeutic Target for Alzheimer’s Disease: A Review

Tsz Yan Fung, Ashok Iyaswamy, Sravan G. Sreenivasmurthy, Senthilkumar Krishnamoorthi, Xin Jie Guan, Zhou Zhu, Cheng Fu Su, Jia Liu, Yuxuan Kan, Yuan Zhang, Hoi Leong Xavier Wong, Min Li

Research output: Contribution to journalReview articlepeer-review


Alzheimer’s disease (AD) is an age-associated neurodegenerative disease; it is the most common cause of senile dementia. Klotho, a single-pass transmembrane protein primarily generated in the brain and kidney, is active in a variety of metabolic pathways involved in controlling neurodegeneration and ageing. Recently, many studies have found that the upregulation of Klotho can improve pathological cognitive deficits in an AD mice model and have demonstrated that Klotho plays a role in the induction of autophagy, a major contributing factor for AD. Despite the close association between Klotho and neurodegenerative diseases, such as AD, the underlying mechanism by which Klotho contributes to AD remains poorly understood. In this paper, we will introduce the expression, location and structure of Klotho and its biological functions. Specifically, this review is devoted to the correlation of Klotho protein and the AD phenotype, such as the effect of Klotho in upregulating the amyloid-beta clearance and in inducing autophagy for the clearance of toxic proteins, by regulating the autophagy lysosomal pathway (ALP). In summary, the results of multiple studies point out that targeting Klotho would be a potential therapeutic strategy in AD treatment.

Original languageEnglish (US)
Article number705
Issue number3
StatePublished - Mar 2022
Externally publishedYes


  • Alzheimer’s disease
  • Klotho
  • autophagy
  • autophagy lysosomal pathway (ALP)
  • neurodegenerative disease

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • General Biochemistry, Genetics and Molecular Biology


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