Therapeutic Intervention at Cellular Quality Control Systems in Alzheimers and Parkinsons Diseases

Abstract

Cellular homeostasis relies on quality control systems so that damaged biologic structures are either repaired or degraded and entirely replaced by newly formed proteins or even organelles. The clearance of dysfunctional cellular structures in long-lived postmitotic cells, like neurons, is essential to eliminate, per example, defective mitochondria, lipofuscin-loaded lysosomes and oxidized proteins. Short-lived proteins are degraded mainly by proteases and proteasomes whether most long-lived proteins and all organelles are digested by autophagy in the lysosomes. Recently, it an interplay was established between the ubiquitin-proteasome system and macroautophagy, so that both degradative mechanisms compensate for each other. In this article we describe each of these clearance systems and their contribution to neuronal quality control. We will highlight some of the findings that provide evidence for the dysfunction of these systems in Alzheimer's and Parkinson's diseases. Ultimately, we provide an outline on potential therapeutic interventions based on the modulation of cellular degradative systems.

Low-Frequency Pulsed Electromagnetic Field Is Able to Modulate miRNAs in an Experimental Cell Model of Alzheimer’s Disease

“…Notably, an alteration of several miRNAs has been related to A β insult [46]. Many other miRNAs are emerging as regulators of the expression not only of APP but also of proteins involved in fundamental cellular processes such as cellular clearance and quality control systems which are altered in AD [47]. Recently, it has been suggested that miRNAs are also able to modulate cognitive and immune processes through direct or indirect alterations of the neuron-to-glia and/or the brain-to-body signaling [48].…”

Mitochondrial metabolism in Parkinson's disease impairs quality control autophagy by hampering microtubule-dependent traffic

“…It is now considered that constitutive basal autophagic activity is a main quality control (QC) process that selectively disposes aberrant protein aggregates and damaged organelles for degradation (9,10). Thus, the regulation of QC autophagy may be critical to restrain the neurodegenerative process (11,12). …”

Achillea millefolium Aqueous Extract does not Impair Recognition Memory in Mice

“…Most neurodegenerative diseases such as Alzheimer, Parkinson, lateral sclerosis and multiple sclerosis have deleterious effect on learning and memory [10] and these diseases mainly destroy integrative and cognitive abilities [10].…”