Chapters authored
The Role of M1- and M2-Type Macrophages in Neurological and Infectious Diseases
Macrophages have a critical role in the outcome of neurological diseases, including neurodegenerative, autoimmune, vascular and microbial diseases. Macrophage role ranges from beneficial to pathogenic depending upon genetics, other components of innate and adaptive immunity, lifestyle and macrophage targets: aggregated molecules or bacterial and viral pathogens. Macrophages are attracted by chemokines to migrate into the brain and remove or inactivate pathogenic molecules. In the patients with neurodegenerative diseases, macrophages target aggregated molecules, amyloid-β1–42 (Aβ) and P-tau in Alzheimer’s disease (AD), and superoxide dismutase-1 (SOD-1) in amyotrophic lateral sclerosis (ALS), but also have autoimmune targets. In AD and ALS patients, macrophages in the pro-resolution M1M2 state are adapted to brain clearance and homeostasis, whereas in the proinflammatory M1 state are modulate to an anti-viral and antibacterial role, which may be associated with collateral damage to tissues. In HIV-1 and CoV2 viral infections, macrophages in M1 state are anti-viral but also pathogenic through inflammatory damage to the heart and the brain. In neurodegenerative diseases, the natural substances polyunsaturated fatty acids (PUFA), vitamins B and D, energy molecules, and flavonoids have beneficial effects on macrophage transcriptome and functions for brain clearance, but the effects are complex and depend on many variables.
Part of the book: Macrophages
The Role of Endoplasmic Reticulum Stress and Its Regulation in the Progression of Neurological and Infectious Diseases
The unfolded protein response (UPR) is a cellular mechanism activated by endoplasmic reticulum (ER) stress, which ranges from inhibition of protein synthesis to apoptosis. ER stress is induced in general by aggregated autologous or foreign (e.g. viral) proteins, oxidative stress, mitochondrial dysfunction, disruption of intracellular calcium, or inflammation. In patients with Alzheimer’s disease (AD) and amyotrophic lateral sclerosis (ALS), the known stressors are aggregated amyloid-beta and superoxide dismutase (SOD-1), respectively, but autologous DNA released by trauma into the cytoplasm may also be involved in ALS. In HIV-1-associated neurocognitive disorders (HAND), ER stress is induced by HIV-1 and antiretroviral therapy. Additionally, in cases of epilepsy, ER stress has been implicated in neuronal dysfunction. In this chapter, we examine a clinical and immunologic approach to ER stress in the progression of neurological and infectious diseases. In addition, we will briefly discuss emerging treatments including omega fatty acids, progesterone, and DHA, which repair and favorably regulate UPR in some patients with neurological diseases.
Part of the book: Updates on Endoplasmic Reticulum