Amino Acids

, Volume 45, Issue 2, pp 269–278

Nardilysin in human brain diseases: both friend and foe

  • H.-G. Bernstein
  • R. Stricker
  • H. Dobrowolny
  • J. Steiner
  • B. Bogerts
  • K. Trübner
  • G. Reiser
Minireview Article


Nardilysin is a metalloprotease that cleaves peptides, such as dynorphin-A, α-neoendorphin, and glucagon, at the N-terminus of arginine and lysine residues in dibasic moieties. It has various functionally important molecular interaction partners (heparin-binding epidermal growth factor-like growth factor, tumour necrosis factor-α-converting enzyme, neuregulin 1, beta-secretase 1, malate dehydrogenase, P42IP4/centaurin-α1, the histone H3 dimethyl Lys4, and others) and is involved in a plethora of normal brain functions. Less is known about possible implications of nardilysin for brain diseases. This review, which includes some of our own recent findings, attempts to summarize the current knowledge on possible roles of nardilysin in Alzheimer disease, Down syndrome, schizophrenia, mood disorders, alcohol abuse, heroin addiction, and cancer. We herein show that nardilysin is a Janus-faced enzyme with regard to brain pathology, being probably neuropathogenic in some diseases, but neuroprotective in others.


Nardilysin Alzheimer disease Schizophrenia Alcoholism Heroin addiction Brain tumour 



Anterior cingulate cortex


Alzheimer disease


A disintegrin and metalloprotease


Amyloid precursor protein


Beta-site APP cleaving enzyme


Central nervous system


Dorso-lateral prefrontal cortex


Down syndrome


Epidermal growth factor


Epidermal growth factor receptor (tyrosine kinase)


Heparin-binding epidermal growth factor-like growth factor


His-Xaa-Xaa-Glu-His zinc–binding motif of the inverzincin/M16 family of metalloproteases






Paraventicular nucleus


Peripheral nervous system


Supraoptic nucleus


Human neuroblastoma cell line


Tumour necrosis factor-α-converting enzyme


Tumour necrosis factor


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Copyright information

© Springer-Verlag Wien 2013

Authors and Affiliations

  • H.-G. Bernstein
    • 1
  • R. Stricker
    • 2
  • H. Dobrowolny
    • 1
  • J. Steiner
    • 1
  • B. Bogerts
    • 1
  • K. Trübner
    • 3
  • G. Reiser
    • 2
  1. 1.Department of PsychiatryOtto-v.-Guericke University MagdeburgMagdeburgGermany
  2. 2.Institute of NeurobiochemistryOtto-v.-Guericke University MagdeburgMagdeburgGermany
  3. 3.Department of PsychiatryInstitute for Legal Medicine, University of Essen-DuisburgEssenGermany

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