Topic: proximity ligation assay

Neurological diseases are complex network-level processes where many aspects of subcellular function undergo depletion, stress, and sometimes catastrophic decline. Conventional single-molecule studies have had limited success in uncovering these highly interconnected events. Our study utilizes network-level modeling with data from mass spectrometry and targeted data from proximity ligation assay to study processes in various synapses of neurological disorders. We aim to measure synaptic signaling across multiple readouts, stimuli, and genetic/aging contexts and use this to build an atlas and m

Parkinson’s disease (PD) is the second most common neurodegenerative disorder worldwide. One of the hallmarks of PD is the alteration in the expression and function of NMDA receptor (NMDAR) and cannabinoid receptor 1 (CB1R). The presence of CB1R-NMDAR complexes has been described in neuronal primary cultures, where the activation of CB1R was suggested to counteract the detrimental NMDAR overactivation in an AD mice model. Thus, we aimed to explore the role of this receptor complex in PD. By using BRET assay, it was demonstrated that a-synuclein induces a reorganization of CB1R-NMDAR complex in

How can short-lived molecules selectively maintain potentiation of synapses to sustain long-term potentiation (late-LTP) and long-term memory? One possibility, suggested by Francis Crick (Nature, 1984), is that continual interaction between synaptic molecules maintains the strengthening of activated synapses in the face of molecular turnover. Here, we tested the hypothesis that continual interaction between KIBRA, a postsynaptic scaffolding protein genetically linked to human memory performance, with the autonomously active, atypical PKC isoform PKMζ, maintains late-LTP and long-term memory. U

Under normal conditions, α-synuclein (αS) is preferentially localized within synaptic boutons. Changes in αS localization may occur, however, as a consequence of a variety of pathophysiological conditions that include increased protein expression. The purpose of this study was to investigate intraneuronal sites of overexpression-induced αS accumulation. In particular, we assessed αS burden within neuronal perikarya and nuclei; the latter analysis was facilitated by a newly developed assay that detected interactions between αS and histones.Experiments were carried out in the substantia pars com

Endoplasmic reticulum-mitochondrial contact sites (ERMCS) play an important role in lipid metabolism, calcium signaling, and autophagy. Disruption of the ERMCS has been reported to be linked to several neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS). However, the etiological role of ERMCS in these diseases remains unclear. We have previously established tyrosine hydroxylase reporter (TH-GFP) iPSC lines from a PD patient with a PRKN mutation for correlative light-electron microscopy (CLEM) analysis and live cell i