<unk>  formation Cytotoxicity caused by<unk><unk>  formation is commonly seen in the world of bacteria. While eukaryotic cells are generally less vulnerable to<unk> -forming toxins because of their larger volume and stiffer, sterol-containing membranes, several eukaryotic<unk> -forming toxins have been seen to sidestep these obstacles by forming especially large, stable<unk><unk> s or anchoring to sterols in the cell membrane. Neurons are particularly vulnerable to<unk> -forming toxins because of their reliance on maintenance of strict Na+, K+, and Ca2+ concentration gradients and membrane potential for proper functioning and action potential propagation. Leakage caused by insertion of an<unk><unk>  such as Aβ rapidly alters intracellular<unk> ic concentrations, resulting in energetic stress, failure of signaling, and cell death.<unk> ic leakage The large, poorly selective, and long-lived nature of Aβ<unk> s allows rapid degradation of membrane potential in neurons. A single Aβ<unk>  4 nS in size can cause Na+ concentration to change as much as 10 μM/s. Degradation of membrane potential in this manner also generates additional Ca2+ influx through voltage-sensitive Ca2+<unk> s in the plasma membrane.<unk> ic leakage alone has been demonstrated to be sufficient to rapidly disrupt cellular homeostasis and induce cell necrosis. Mitochondrial pathway of apoptosis Aβ<unk> s may also trigger apoptosis through insertion in mitochondrial membranes. Aβ injection in rats has been shown to damage mitochondrial structure in neurons, decrease mitochondrial membrane potential, and increase intracellular Ca2+ concentration. Additionally, Aβ accumulation increases expression of genes associated with the mitochondrial permeability transition pore (MPTP), a non-selective, high conductance<unk>  spanning the inner and outer mitochondrial membrane. Ca2+ influx into mitochondria can collapse mitochondrial membrane potential, causing MPTP opening, which then induces mitochondrial swelling, further dissipation of membrane potential, generation of mitochondrial reactive oxygen species (ROS), rupture of the outer mitochondrial membrane, and release of apoptogenic factors such as cytochrome c.
Ion channel hypothesis of Alzheimer's disease
Variably protease-sensitive prionopathy
Psychological therapies for dementia
Limbic-predominant age-related TDP-43 encephalopathy
Biochemistry of Alzheimer's disease
Glutamate hypothesis of schizophrenia
Synucleinopathy
Frontotemporal dementia and parkinsonism linked to chromosome 17