The Beta Amyloid Core Hexapeptide Protects Against Full-Length Beta Amyloid-Induced Alteration of Dendritic Spine Morphology and Density.

Pathological levels of beta amyloid (Aβ) lead to disruption and elimination of synapses in brain as the result of direct neurotoxicity as well as neuroinflammation. The synaptic impact of beta amyloid includes altered morphology and reduced number of dendritic spines at excitatory synapses, evident in the brains of individuals with Alzheimer's disease. Here, we assessed the ability of an identified neuroprotective peptide, YEVHHQ, derived from the N-terminal domain of Aβ, known as the AβCore, to protect against Aβ-induced alterations in dendritic spines.

The neuroprotective N-terminal amyloid-β core hexapeptide reverses reactive gliosis and gliotoxicity in Alzheimer's disease pathology models.

Background: Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by accumulation of extracellular amyloid beta (Aβ) and intracellular neurofibrillary tangles, leading to chronic activation of astrocytes and microglia and persistent neuroinflammation. Aβ-linked activation of microglia and astrocytes leads to increased intracellular calcium and production of proinflammatory cytokines, impacting the progression of neurodegeneration. An N-terminal Aβ fragment (Aβ) and a shorter hexapeptide core sequence within the N-Aβ fragment (N-Aβcore: Aβ) have previously been shown to protect against Aβ-induced mitochondrial dysfunction, oxidative stress and apoptosis in neurons and rescue synaptic and spatial memory deficits in an APP/PSEN1 mouse model.

Fluctuation Imaging of LRRK2 Reveals that the G2019S Mutation Alters Spatial and Membrane Dynamics.

Mutations within the gene are the most common genetic cause of autosomal and sporadic Parkinson's disease (PD). LRRK2 is a large multidomain kinase that has reported interactions with several membrane proteins, including Rab and Endophilin, and has recently been proposed to function as a regulator of vesicular trafficking. It is unclear whether or how the spatiotemporal organization of the protein is altered due to LRRK2 activity.