Cdk5 at crossroads of protein oligomerization in neurodegenerative diseases: facts and hypotheses

作者：Wilkaniec Anna; Czapski Grzegorz A; Adamczyk Agata

来源：Journal of Neurochemistry, 2016, 136(2): 222-233.

DOI：10.1111/jnc.13365

<jats:title>Abstract</jats:title><jats:sec><jats:label /><jats:p>Cyclin‐dependent kinase 5 (Cdk5) is involved in proper neurodevelopment and brain function and serves as a switch between neuronal survival and death. Overactivation of Cdk5 is associated with many neurodegenerative disorders such as Alzheimer's or Parkinson's diseases. It is believed that in those diseases Cdk5 may be an important link between disease‐initiating factors and cell death effectors. A common hallmark of neurodegenerative disorders is incorrect folding of specific proteins, thus leading to their intra‐ and extracellular accumulation in the nervous system. Abnormal Cdk5 signaling contributes to dysfunction of individual proteins and has a substantial role in either direct or indirect interactions of proteins common to, and critical in, different neurodegenerative diseases. While the roles of Cdk5 in α‐synuclein (<jats:styled-content style="fixed-case">ASN</jats:styled-content>) – tau or β‐amyloid peptide (Aβ) – tau interactions are well documented, its contribution to many other pertinent interactions, such as that of <jats:styled-content style="fixed-case">ASN</jats:styled-content> with Aβ, or interactions of the Aβ – <jats:styled-content style="fixed-case">ASN</jats:styled-content> – tau triad with prion proteins, did not get beyond plausible hypotheses and remains to be proven. Understanding of the exact position of Cdk5 in the deleterious feed‐forward loop critical for development and progression of neurodegenerative diseases may help designing successful therapeutic strategies of several fatal neurodegenerative diseases.</jats:p></jats:sec><jats:sec><jats:label /><jats:p>
<jats:boxed-text content-type="graphic" position="anchor"><jats:graphic xmlns:xlink="http://www.w3.org/1999/xlink" mimetype="image/png" position="anchor" specific-use="enlarged-web-image" xlink:href="graphic/jnc13365-fig-0004-m.png"><jats:alt-text>image</jats:alt-text></jats:graphic></jats:boxed-text>
Cyclin‐dependent kinase 5 (Cdk5) is associated with many neurodegenerative disorders such as Alzheimer's or Parkinson's diseases. It is believed that in those diseases Cdk5 may be an important factor involved in protein misfolding, toxicity and interaction. We suggest that Cdk5 may contribute to the vicious circle of neurotoxic events involved in the pathogenesis of different neurodegenerative diseases.</jats:p></jats:sec>

• 出版日期2016-1