## 5 Neurodegenerative Diseases and Environmental Factors  
Neurodegenerative diseases pose a significant public health challenge, affecting millions of individuals globally. This group of disorders, which includes Alzheimer's disease (AD), Amyotrophic Lateral Sclerosis (ALS), Huntington's disease (HD), and Parkinson's disease (PD), among others, presents symptoms such as memory loss, impaired motor function, and cognitive decline. The hallmark of these diseases is the progressive loss of neurons in the central and/or peripheral nervous system [85]. While genetic factors have long been associated with these conditions, research underscores the crucial role of environmental influences in their onset and progression. For instance, while the causes of ALS are largely unknown, approximately 5 to 20% of cases (familial cases) have been linked to mutations in identified genes. However, for the remaining 95-80% of cases (sporadic cases), a combination of genetic and environmental factors likely contributes to disease development [86; 87; 88]. Potential environmental determinants include, but are not limited to, exposure to cyanotoxins, electromagnetic fields, and various chemicals such as pesticides, solvents, heavy metals, and selenium. Studies have investigated the association between traffic-related air pollution and increased ALS risk in the US, as well as the impact of long-term exposure to air pollutants like PM\({}_{2.5}\), NOx, and NO\({}_{2}\) on ALS risk [89]. Emerging evidence also suggests that exposure to air pollution, which contains components like ultrafine particulate matter (UFPM), could contribute to neurodegenerative diseases such as AD, PD, Multiple Sclerosis (MS), and Motor Neuron Diseases (MND), although the evidence remains inconsistent and limited for MS and MND [90]. While the exact mechanisms are still under study, both animal and epidemiological research indicate that air pollution exposure may induce oxidative stress, leading to neurotoxicity and neuroinflammation [91; 92]. In addition to animal and epidemiological studies on air pollutants and brain impairment, data from in vitro models of target tissues, such as cells of the olfactory mucosa, support the implications of air pollutants in neurodegeneration. Indeed, a key route for particles entry into the brain is through the olfactory epithelium [93]. Recent research has examined the metal content in various environmental compartments and the genetic contribution to ALS among patients living in specific areas [94]. In these areas, metal contaminants have been found to exceed the legal limits in surface water, wastewater, and soil, supporting the hypothesis that increased ALS incidence may be linked to environmental metal(loids) contamination along with other environmental factors. In addition, and further supporting these findings, biomonitoring studies describe how heavy metals are significantly found in the neurons of patients affected by motor neuron disease in comparison to controls [95; 96]. Interestingly, MPs in the environment are rapidly colonized by bacteria, cyanobacteria, and microalgae, forming biofilms that alter their surface chemistry and attract environmental metals. Exposure to metal-MPs biofilms can disrupt cell homeostasis, leading to toxicities. Consequently, imbalances in metal concentrations can result in neuronal network dysfunction; reactive oxygen species (ROS) production; and mitochondrial damage in diseases such as PD, AD, and Prion disorder [97]. Mechanisms of Plastic Particles' Transfer to the Central Nervous System (CNS) and Effects on the Blood-Brain Barrier  
Exposure of humans to plastic particles has been estimated to account for over hundreds of thousands particle/year and to accumulate at various concentrations in different tissues and organs such as the skin, heart, blood, testis, and intestine, among others, exhibiting the ability to accumulate into internal organs/tissues thanks to their ability to pass through epithelial barriers, as was recently reviewed by [PERSON] et al. [65].