RYR3

Increased risk of neurodegenerative diseases has been envisaged for air pollution exposure. On the other hand, environmental risk factors, including air pollution, have been suggested for Amyotrophic Lateral Sclerosis (ALS) pathomechanism. Therefore, the neurotoxicity of ultrafine particulate matter (PM0.1) (PM < 0.1 μm size) and its sub-20 nm nanoparticle fraction (NP20) has been investigated in motor neuronal-like cells and primary cortical neurons, mainly affected in ALS. The present data showed that PM0.1 and NP20 exposure induced endoplasmic reticulum (ER) stress, as occurred in cortex and spinal cord of ALS mice carrying G93A mutation in SOD1 gene. Furthermore, NSC-34 motor neuronal-like cells exposed to PM0.1 and NP20 shared the same proteomic profile on some apoptotic factors with motor neurons treated with the L-BMAA, a neurotoxin inducing Amyotrophic Lateral Sclerosis/Parkinson-Dementia Complex (ALS/PDC). Of note ER stress induced by PM0.1 and NP20 in motor neurons was associated to pathological changes in ER morphology and dramatic reduction of organellar Ca²⁺ level through the dysregulation of the Ca²⁺-pumps SERCA2 and SERCA3, the Ca²⁺-sensor STIM1, and the Ca²⁺-release channels RyR3 and IP3R3. Furthermore, the mechanism deputed to ER Ca²⁺ refilling (e.g. the so called store operated calcium entry-SOCE) and the relative currents ICRAC were also altered by PM0.1 and NP20 exposure. Additionally, these carbonaceous particles caused the exacerbation of L-BMAA-induced ER stress and Caspase-9 activation. In conclusion, this study shows that PM0.1 and NP20 induced the aberrant expression of ER proteins leading to dysmorphic ER, organellar Ca²⁺ dysfunction, ER stress and neurotoxicity, providing putative correlations with the neurodegenerative process occurring in ALS.

Shiga toxin (stx), produced by enterohemorrhagic Escherichia coli (EHEC) or Shigella, causes hemolytic uremic syndrome (HUS) in humans. EHEC-mediated illnesses are recommended to treat by immune supportive strategies, instead of antibiotic therapy. Widely used probiotic Lactobacillus casei produces many bioactive metabolites, i.e., conjugated linoleic acids (CLAs) which have potential to educate host immunity and control EHEC growth and expression of its virulence genes. In this study, it was found that total metabolites of L. casei exerted a protective effect on Gb₃ receptor containing mammalian cells against stx exposure.

Cell-fate decisions depend on the precise and strict regulation of multiple signaling molecules and transcription factors, especially intracellular Ca²⁺ homeostasis and dynamics. Type 3 inositol 1,4,5-triphosphate receptor (IP3R3) is an a tetrameric channel that can mediate the release of Ca²⁺ from the endoplasmic reticulum (ER) in response to extracellular stimuli. The gating of IP3R3 is regulated not only by ligands but also by other interacting proteins. To date, extensive research conducted on the basic structure of IP3R3, as well as its regulation by ligands and interacting proteins, has provided novel perspectives on its biological functions and pathogenic mechanisms. This review aims to discuss recent advancements in the study of IP3R3 and provides a comprehensive overview of the relevant literature pertaining to its structure, biological functions, and pathogenic mechanisms.