Role of chaperone-mediated autophagy in the pathophysiology including pulmonary disorders

Hosaka, Yusuke; Araya, Jun; Fujita, Yu; Kuwano, Kazuyoshi

doi:10.1186/s41232-021-00180-9

Cited by 19 publications

(22 citation statements)

References 69 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is possible that posttranslational changes such as deamination can result in KFERQ-like sequences in some proteins. 3 …”

Section: Chaperone‑mediated Autophagy (Cma)mentioning

confidence: 99%

“… 6 It is responsible for substrate binding and internalization to lysosomes, and thus, the lysosomal expression level of LAMP2A is a rate-limiting factor for CMA. 3 …”

Section: Chaperone‑mediated Autophagy (Cma)mentioning

confidence: 99%

“…Both soluble lysosomal hydrolases (eg, proteases, lipases, glycosidases, and nucleases) and lysosomal membrane proteins (eg, lysosome associated membrane proteins) are necessary for lysosome function. 3 …”

Section: Chaperone‑mediated Autophagy (Cma)mentioning

confidence: 99%

“…LAMP2A levels and conformational status are crucial, and this is a rate-limiting phase in the process that can be changed through synthesis, degradation, and redistribution. 3

Figure 2 The process of CMA: (1) recognizing substrate proteins and targeting them to lysosome; (2) binding and unfolding substrate proteins; (3) multimerization of LAMP-2A and HSP90 binds to LAMP2A to stabilize it while it organizes into higher molecular weight complexes (4) translocation into lysosomes, substrate translocation mediated by lysosomal HSC70 (lys-HSC70) (5) degradation by lysosome hydrolytic enzymes (6) once substrate translocation is complete, LAMP2A dissociates into monomers in a process dependent on cytosolic HSC70. Created with BioRender.com.…”

Section: Chaperone‑mediated Autophagy (Cma)mentioning

confidence: 99%

“…Autophagy is a highly conserved mechanism for delivering cytoplasmic components for lysosomal degradation in order to maintain the homeostatic balance of cellular protein and organelle synthesis, degradation, and recycling. 3 Autophagy is classified into three types: macroautophagy (MA), microautophagy (MA), and chaperone-mediated autophagy (CMA). 4 , 5 …”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Chaperone-Mediated Autophagy and Its Implications for Neurodegeneration and Cancer

Assaye¹,

Gizaw²

2022

IJGM

View full text Add to dashboard Cite

Proteostasis, also known as protein homeostasis, is critical for cell survival. Autophagy is a cellular process that degrades and recycles damaged or long-lived proteins, misfolded proteins, and damaged or abnormal organelles in order to preserve homeostasis. Among the three forms of autophagy, chaperone-mediated autophagy (CMA) is distinct from macroautophagy and microautophagy; it does not require the formation of vacuoles and only degrades selected individual proteins. CMA helps to maintain cellular homeostasis by regulating protein quality, bioenergetics, and substrate-associated cellular processes at the right moment. This pathway’s dysfunction has been linked to several diseases and disorders. Neurodegenerative diseases and cancer have received the most attention. In various neurodegenerative disorders, especially in their later stages, CMA activity declines. CMA has been shown to act as a tumor suppressor in cancer by destroying specific tumor promoters. Once a tumor has grown, it also helps tumor survival and the metastatic cascade. The presence of changes in CMA in these diseases disorders raises the idea of targeting CMA to restore cellular homeostasis as a potential therapeutic method. Manipulation of CMA activity may be effective therapeutic strategies for treating these diseases. Therefore, in this paper; we introduce the basic processes, regulatory mechanisms, and physiological functions of CMA; evidences supporting the role of impaired CMA function in neurodegeneration and cancer; and the potential of how targeting CMA could be a promising therapeutic method for the two diseases.

show abstract

“…It is possible that posttranslational changes such as deamination can result in KFERQ-like sequences in some proteins. 3 …”

Section: Chaperone‑mediated Autophagy (Cma)mentioning

confidence: 99%

“… 6 It is responsible for substrate binding and internalization to lysosomes, and thus, the lysosomal expression level of LAMP2A is a rate-limiting factor for CMA. 3 …”

Section: Chaperone‑mediated Autophagy (Cma)mentioning

confidence: 99%

Section: Chaperone‑mediated Autophagy (Cma)mentioning

confidence: 99%

“…LAMP2A levels and conformational status are crucial, and this is a rate-limiting phase in the process that can be changed through synthesis, degradation, and redistribution. 3

Section: Chaperone‑mediated Autophagy (Cma)mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Chaperone-Mediated Autophagy and Its Implications for Neurodegeneration and Cancer

Assaye¹,

Gizaw²

2022

IJGM

View full text Add to dashboard Cite

show abstract

The Antipsychotic Drug Aripiprazole Suppresses Colorectal Cancer by Targeting LAMP2a to Induce RNH1/miR‐99a/mTOR‐Mediated Autophagy and Apoptosis

Hu,

Fu,

Han

et al. 2024

Advanced Science

View full text Add to dashboard Cite

The mammalian target of rapamycin (mTOR) is a critical signaling hub for sustaining cancer survival. Targeting mTOR and inducing autophagic cell death downstream of it represent promising therapeutic strategies for cancer prevention. A US Food and Drug Administration‐approved drug library containing 616 small molecules is used to screen anticancer drugs against colorectal cancer (CRC) cells that rely on mTOR. This led to the identification of an antipsychotic drug aripiprazole, which significantly induced mTOR inhibition and autophagic apoptosis in CRC, in vitro and in vivo. The use of drug affinity response target stability identified lysosome‐associated membrane protein 2A (LAMP2a) as a direct target of aripiprazole. LAMP2a‐deficient CRC cells are refractory to aripiprazole. High LAMP2a expression is associated with poor survival of patients with CRC and negatively correlated with expression of ribonuclease inhibitor 1 (RNH1), which is later confirmed as a novel substrate of LAMP2a. Mechanistically, aripiprazole bound to the Lys401–His404 of LAMP2a and repressed its activity, subsequently inactivating RNH1/miR‐99a/mTOR signaling and inducing autophagy‐mediated apoptosis, thereby suppressing tumorigenesis. Liposome‐mediated delivery of aripiprazole in combination with fluorouracil elicited superior therapeutic benefits in CRC, as compared to single treatments, thereby highlighting that aripiprazole may be repurposed as a novel therapeutic agent for CRC treatment.

show abstract

Two autophagy-related proteins, ATG5 and ATG7, from Eriocheir sinensis involved into Spiroplasma eriocheiris infection

Yao,

Meng,

et al. 2024

Aquaculture

View full text Add to dashboard Cite

Role of chaperone-mediated autophagy in the pathophysiology including pulmonary disorders

Cited by 19 publications

References 69 publications

Chaperone-Mediated Autophagy and Its Implications for Neurodegeneration and Cancer

Chaperone-Mediated Autophagy and Its Implications for Neurodegeneration and Cancer

The Antipsychotic Drug Aripiprazole Suppresses Colorectal Cancer by Targeting LAMP2a to Induce RNH1/miR‐99a/mTOR‐Mediated Autophagy and Apoptosis

Two autophagy-related proteins, ATG5 and ATG7, from Eriocheir sinensis involved into Spiroplasma eriocheiris infection

Contact Info

Product

Resources

About