Speaker
Description
Abstract. Alzheimer’s disease is a neurological disorder characterised by the abnormal accumulation of the proteins including amyloid beta and neurofibrillary tangles, and is closely associated with gradual increase in mitochondrial viscosity. Amyloid-β protein produced during the amyloid cascade interacts with metal ions, disrupts electron transport chain (ETC) complex assembly, and alters Ca²⁺ homeostasis, leading to amplified generation of reactive oxygen species (ROS). These ROS trigger peroxidation of polyunsaturated fatty acids present in the mitochondrial membrane, transforming them into aldehydes such as 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA). These aldehydes promote cross-linking of protein and lipid molecules, resulting in membrane stiffening and increased viscosity. Although, viscosity plays a vital role in disease progression, measuring minute viscosity variations in vivo remains challenging due to the presence of competing biological factors. Here, we show that a planar, symmetrical two-photon fluorescent molecular rotor, L-Probe, can selectively monitor microenvironmental viscosity through changes in fluorescence emission intensity arising from restricted molecular motion. The mitochondria-specific L-Probe exhibited an increase in fluorescence emission upon incubation in Aβ- and Cu²⁺-spiked Alzheimer’s disease cellular models. In addition, in vivo studies using APP/PS1 mice are expected to show clear mitochondrial viscosity variations owing to the two-photon fluorescence imaging capability of L-Probe. As a highly sensitive and selective probe for mitochondrial viscosity measurement, L-Probe is anticipated to open new avenues in molecular engineering within the field of chemistry. Furthermore, this study may help researchers to gain mechanistic insights into relationship between the mitochondrial health and related Alzheimer’s disease pathology.
