Article

JNK3 as a Therapeutic Target for Neurodegenerative Diseases

Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy.
Journal of Alzheimer's disease: JAD (Impact Factor: 4.15). 02/2011; 24(4):633-42. DOI: 10.3233/JAD-2011-091567
Source: PubMed

ABSTRACT

c-Jun N-terminal kinases (JNKs) and in particular JNK3 the neuronal specific isoform, have been recognized as important enzymes in the pathology of diverse neurological disorders. Indeed, several efforts have been made to design drugs that inhibit JNK signaling. The success that characterized the new generation of cell permeable peptides raise the hope in the field of neurodegeneration for new therapeutic routes. However, in order to design new and more efficient therapeutical approaches careful re-examination of current knowledge is required. Scaffold proteins are key endogenous regulators of JNK signaling: they can modulate spatial and temporal activation of the JNK signaling and can thus provide the basis for the design of more specific inhibitors. This review focuses on delineating the role of scaffold proteins on the regulation of JNK signaling in neurons. Furthermore the possibility to design a new JNK3 cell permeable peptide inhibitor by targeting the β-arrestin-JNK3 interaction is discussed.

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    • "oid lupus erythematous as well as D - JNKi1 for the treatment of inflammation and stroke ( as reviewed by Koch et al . , 2015 ) . In the following sections , and represented in Tables 1 and 2 and Figure 3 , current knowledge of the JNK inhibitors will be described ( Bogoyevitch et al . , 2004 ; Wang et al . , 2004 ; Bogoyevitch and Arthur , 2008 ; Antoniou et al . , 2011 ) ."
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    • "Thus, much attention has been paid to the design of new inhibitors of this kinase family for the treatment of malignant disorders (Pratilas and Solit, 2010; Santarpia et al., 2012). JNK3 is predominantly expressed in the brain, testes, and heart (Bode and Dong, 2007), and its specific inhibition is able to inhibit neurodegenerative diseases in animal models (Parkinson and Alzheimer diseases) (Antoniou et al., 2011). JNK1 and JNK2 are ubiquitously expressed in tissues and can present with similar or different functions (Davis, 2000). "
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