Translational Shift of HSP90 as a Novel Therapeutic Target from Cancer to Neurodegenerative Disorders: An Emerging Trend in the Cure of Alzheimer's and Parkinson's Diseases (E-pub Ahead of Print)
Mohammad Zubair Alam,
Khalid Hussain Wali Sait,
Abdul Wahab Noorwali,
Mohd Sajjad Ahmad Khan,
Mohammad A. Kamal,
Parkinson's disease (PD) is considered as the second most common neurodegenerative disorder after Alzheimer's disease (AD). Despite having extensive research, the apparent pathogenic mechanism of these neurodegenerative disorders has not yet been fully understood. Recently, a ubiquitous molecular chaperone known as Heat Shock Protein 90 (HSP90) has been shown to play a key role in averting protein mis-folding and involves in assisting immature protein aggregation through inhibition of apoptotic activity in neuro-inflammatory disease. Hence, HSP90 has been classified as a potent protein potentially involved in AD and PD pathogenesis. The latest research from various laboratories have confirmed its role in maintaining aberrant neuronal protein’s functional stability to a great capacity.
Additionally, HSP90 also involve in regulating the activity of the heat shock factor-1 (HSF-1), a transcription factor known to be master regulator of the heat shock response mechanism that cells employ in order to protect them against stress conditions. Owing to this inherent chaperon functional quality makes the HSP90 as an ideal candidate for novel inhibitory target as a dual therapeutic modality in neurodegenerative disorders. HSP90 inhibition lead to suppress atypical neuronal activity by assisting in improving protein aggregation and its related toxicity. Further, HSP90 inhibitors may redirect neuronal aggregate formation, and protect against protein toxicity by HSF-1 activation and subsequent induction of HSP70 in AD. This review is designed in order to discuss the role of HSP90 in neurodegeneration and its potential outcome in targeting HSP90 by inhibitors in neurodegenerative diseases, particularly in AD and PD. Moreover, this review will provide more insight into the recent advancements and challenges in targeting HSP90 for AD and PD management.
Keywords: Heat shock protein, HSP90, HSP70, HSP27, AD, PD
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