Combustion and friction-derived nanoparticles and industrial-sourced nanoparticles: The culprit of Alzheimer and Parkinson's diseases

Abstract

Redox-active, strongly magnetic, combustion and friction-derived nanoparticles (CFDNPs) are abundant in particulate matter air pollution. Urban children and young adults with Alzheimer disease Continuum have higher numbers of brain CFDNPs versus clean air controls. CFDNPs surface charge, dynamic magnetic susceptibility, iron content and redox activity contribute to ROS generation, neurovascular unit (NVU), mitochondria, and endoplasmic reticulum (ER) damage, and are catalysts for protein misfolding, aggregation and fibrillation. CFDNPs respond to external magnetic fields and are involved in cell damage by agglomeration/clustering, magnetic rotation and/or hyperthermia. This review focus in the interaction of CFDNPs, nanomedicine and industrial NPs with biological systems and the impact of portals of entry, particle sizes, surface charge, biomolecular corona, biodistribution, mitochondrial dysfunction, cellular toxicity, anterograde and retrograde axonal transport, brain dysfunction and pathology. NPs toxicity information come from researchers synthetizing particles and improving their performance for drug delivery, drug targeting, magnetic resonance imaging and heat mediators for cancer therapy. Critical information includes how these NPs overcome all barriers, the NPs protein corona changes as they cross the NVU and the complexity of NPs interaction with soluble proteins and key organelles. Oxidative, ER and mitochondrial stress, and a faulty complex protein quality control are at the core of Alzheimer and Parkinson's diseases and NPs mechanisms of action and toxicity are strong candidates for early development and progression of both fatal diseases. Nanoparticle exposure regardless of sources carries a high risk for the developing brain homeostasis and ought to be included in the AD and PD research framework.

Keywords: Agglomeration; Air pollution; Alpha-synuclein; Alzheimer disease continuum in children and young adults; Brain magnetite/maghemite; Combustion and friction derived nanoparticles; Endothelial damage; External magnetic fields; Fibrillation; Misfolded proteins; Mitochondrial and endoplasmic reticulum stress; Nanoparticles; Neurovascular unit; Oxidative stress; Parkinson; Transition metals.