Metal imaging in neurodegenerative diseases

Abstract

Metal ions are known to play an important role in many neurodegenerative diseases including Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and prion diseases. In these diseases, aberrant metal binding or improper regulation of redox active metal ions can induce oxidative stress by producing cytotoxic reactive oxygen species (ROS). Altered metal homeostasis is also frequently seen in the diseased state. As a result, the imaging of metals in intact biological cells and tissues has been very important for understanding the role of metals in neurodegenerative diseases. A wide range of imaging techniques have been utilized, including X-ray fluorescence microscopy (XFM), particle induced X-ray emission (PIXE), energy dispersive X-ray spectroscopy (EDS), laser ablation inductively coupled mass spectrometry (LA-ICP-MS), and secondary ion mass spectrometry (SIMS), all of which allow for the imaging of metals in biological specimens with high spatial resolution and detection sensitivity. These techniques represent unique tools for advancing the understanding of the disease mechanisms and for identifying possible targets for developing treatments. In this review, we will highlight the advances in neurodegenerative disease research facilitated by metal imaging techniques.

Curcumin abates hypoxia-induced oxidative stress based-ER stress-mediated cell death in mouse hippocampal cells (HT22) by controlling Prdx6 and NF-κB regulation

“…Recently, an inverse correlation between antioxidant levels and neuronal cell injury and malfunction has been reported (7,24,43,82). However, the physiological role of antioxidants depends on their levels of expression and activity in cells.…”

Techniques for measuring cellular zinc

“…LA-ICP-MS has been widely applied in the life sciences for analyzing biological samples for metal localization in medical studies, such as tumor growth analysis, and biochemistry of animal model diseases [13, 39]. This method uses high-energy focused lasers to ablate particles from a solid sample; the particles are then carried by gas (Ar or He) into an ICP-MS platform where ionization occurs and charged ions are detected by their mass-to-charge ratio.…”

Quantification estimate methods for synchrotron radiation X-ray fluorescence spectroscopy

“…The probed volume by the incident X-ray beam in this regime can be characterized by the mean free path, which is the average distance an X-ray would travel into the material. The mean free path is calculated for any material using (6), where PðxÞ is the probability of an incident photon not interacting with the surrounding material over a distance x. The mean free path for the sample and the reference will equal the inverse of the product of the total mass attenuation coefficient and the density for that material:…”

“…To obtain further insight or to maintain biological or medical relevance quantifying these localized elemental concentrations is becoming increasingly important [2][3][4][5][6]. Traditionally XRF has been combined with quantification methods such as inductively coupled plasma mass spectrometry (ICP-MS) [7] and laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) [8].…”