Publication

DNAJ Proteins and Protein Aggregation Diseases

Kakkar, V., Prins, L. C. B. & Kampinga, H. H., Nov-2012, In : Current topics in medicinal chemistry. 12, 22, p. 2479-2490 12 p.

Research output: Contribution to journalReview articleAcademicpeer-review

Many neurodegenerative diseases are late onset diseases, associated with aggregation of proteins, implying that aged cells are more susceptible to proteotoxic stress. It is known that with aging, there is a decline in the functionality of chaperone networks and on the other hand, accumulation of damaged proteins occurs. Together, this has a cumulative effects on cellular protein homeostasis. Several studies have revealed that availability of DNAJ proteins, the co-chaperones to the Hsp70 machine, could be a rate-limiting factor in handling diseased proteins within the cell. In this review, we highlight how DNAJ proteins can affect aggregation of disease-causing proteins, if and how this depends on their function as Hsp70 co-chaperones, and how much this depends on the type of protein causing the disease. Finally, we will discuss the five known degenerative diseases that are linked to mutations in individual DNAJ members and what mechanism may underlie these DNAJ chaperonopathies.

Original languageEnglish
Pages (from-to)2479-2490
Number of pages12
JournalCurrent topics in medicinal chemistry
Volume12
Issue number22
Publication statusPublished - Nov-2012

    Keywords

  • Protein aggregation diseases, DNAJ proteins, neurodegeneration, Hsp70, chaperonopathies, protein quality control, HEAT-SHOCK-PROTEIN, RECESSIVE SPASTIC ATAXIA, HEREDITARY MOTOR NEUROPATHY, DEPENDENT REACTION CYCLE, MOLECULAR CHAPERONES, POLYGLUTAMINE TOXICITY, CHARLEVOIX-SAGUENAY, INCLUSION FORMATION, CSP-ALPHA, IN-VITRO

ID: 5812710