Abstract
Proteins play crucial and diverse roles within the cell. To exert their biological function they must fold to acquire an appropriate three-dimensional conformation. Once their function is fulfilled, they need to be properly degraded to hamper any possible damage. Protein homeostasis or proteostasis comprises a complex interconnected network that regulates different steps of the protein quality control, from synthesis and folding, to degradation. Due to the primary role of proteins in cellular function, the integrity of this network is critical to assure functionality and health across lifespan. Proteostasis failure has been reported in the context of aging and neurodegeneration, such as Alzheimer’s and Parkinson’s disease. Therefore, targeting the proteostasis elements emerges as a promising neuroprotective therapeutic approach to prevent or ameliorate the progression of these disorders. A variety of natural products are known to be neuroprotective by protein homeostasis interaction. In this review, we will focus on the current knowledge regarding the use of natural products as modulators of different components of the proteostasis machinery within the framework of age-associated neurodegenerative diseases.
Highlights
The proteostasis network is composed of a series of interconnected elements that assure correct protein functionality and degradation [1]
There is no consensus in the field regarding the molecular mechanisms that explain their augmented incidence in the elderly brain, a common feature of all these diseases is the accumulation of abnormal protein aggregates in the form of oligomers and inclusions, suggesting that general mechanisms controlling proteostasis may underlay the etiology of these diseases [4]
A multitude of studies have study the effect of olive oil in combination with Mediterranean diet in an effort to evaluate its effect in patients with cognitive decline and dementia [89], including Alzheimer’s disease (AD) and Parkinson disease (PD), but none of them analyzed the capability of oleuropein aglycone to cross the blood-brain barrier (BBB), tolerance, biodistribution or its effect in treating neurodegenerative disorders
Summary
The proteostasis network is composed of a series of interconnected elements that assure correct protein functionality and degradation [1]. Functional studies indicate that altered proteostasis at the level of the ER is one of the major contributors to aging [4,13] Several harmful stimuli, such oxidative stress and disturbances in the secretory pathway may lead to accumulation of unfolded or misfolded proteins at the ER lumen, activating the ER stress response [14]. Several intrinsic and extrinsic factors that alter proteostasis cause a decreased protein quality control, contributing to the accumulation of damaged proteins If not rescued, this condition can lead to protein misfolding disorders, such as AD and PD [19,20,21,22,23]. One can conclude that boosting up the elements of the proteostasis machinery is a promising broad-spectrum therapeutic approach, with the potential to treat or revert age-associated neurodegeneration, but a variety of protein misfolding disorders
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