Neuronal and microglial cathepsins in aging and age-related diseases

Hiroshi Nakanishi

Research output: Contribution to journalReview article

97 Citations (Scopus)

Abstract

It has been long believed that cathepsins compensate for each other because of their overlapping substrate specificities. However, there is increasing evidence that disturbance of the normal balance of their enzymatic activities is the first insult in brain aging and age-related diseases. The imbalance of cathepsins may further cause age-related neuropathological changes such as accumulation of autophagic vacuoles and the formation of ceroid-lipofuscin leading to neuronal dysfunction and damage. Leakage of cathepsins due to the fragility of lysosomal membranes during aging also contributes to neurodegeneration. Furthermore, the deficiency of cathepsin D has been recently revealed to provoke a novel type of lysosomal storage disease associated with massive neurodegeneration. In these animals, microglia are activated to initiate inflammatory and cytotoxic responses by binding and phagocytosis of storage neurons. Activated microglia also release some members of cathepsins to induce neuronal death by degrading extracellular matrix proteins. Thus the microglial activation possibly through sensing neuronal storage may also be an important causative factor for neurodegeneration in lysosomal storage diseases and age-related diseases such as Alzheimer's disease. This review describes the pathological roles of neuronal and microglial cathepsins in brain aging and age-related diseases.

Original languageEnglish
Pages (from-to)367-381
Number of pages15
JournalAgeing Research Reviews
Volume2
Issue number4
DOIs
Publication statusPublished - Jan 1 2003

Fingerprint

Cathepsins
Aging of materials
Lysosomal Storage Diseases
Microglia
Ceroid
Brain
Lipofuscin
Cathepsin D
Extracellular Matrix Proteins
Substrate Specificity
Vacuoles
Phagocytosis
Alzheimer Disease
Neurons
Animals
Chemical activation
Membranes
Substrates

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biochemistry
  • Ageing
  • Molecular Biology
  • Neurology

Cite this

Neuronal and microglial cathepsins in aging and age-related diseases. / Nakanishi, Hiroshi.

In: Ageing Research Reviews, Vol. 2, No. 4, 01.01.2003, p. 367-381.

Research output: Contribution to journalReview article

Nakanishi, Hiroshi. / Neuronal and microglial cathepsins in aging and age-related diseases. In: Ageing Research Reviews. 2003 ; Vol. 2, No. 4. pp. 367-381.
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