The absence of Parkin in hTau mice leads to synaptic mitochondrial dysfunction, alterations to the synaptic proteome, and increased phosphorylated tau in the Hippocampus.

Amongst the major histopathological hallmarks in Alzheimer's disease are intracellular neurofibrillary tangles consisting of hyperphosphorylated and aggregated Tau, synaptic dysfunction, and synapse loss. We have previously shown evidence of synaptic mitochondrial dysfunction in a mouse model of Tauopathy that overexpresses human Tau (hTau). Here, we questioned whether the levels or activity of Parkin, an E3 ubiquitin ligase involved in mitophagy, can influence Tau-induced synaptic mitochondrial dysfunction.

Microenvironmental conditions and serum availability alter primary human macrophage NF-κB inflammatory response and function.

Macrophages are central to innate immunity and are routinely used in vitro to examine molecular mechanisms contributing to innate immune signaling. However, there is a lack of consensus within the field for optimal in vitro culturing methods, and it is not well understood whether differences in culture conditions produce incongruent outcomes. Here, we compared the effects of commonly used culture medium compositions on TLR4-mediated proinflammatory activity in primary human monocyte-derived macrophages (hMDMs) isolated from healthy blood donors.

Tau association with synaptic mitochondria coincides with energetic dysfunction and excitatory synapse loss in the P301S tauopathy mouse model.

Neurodegenerative Tauopathies are a part of several neurological disorders and aging-related diseases including, but not limited to, Alzheimer's Disease, Frontotemporal Dementia with Parkinsonism, and Chronic Traumatic Encephalopathy. The major hallmarks present in these conditions include Tau pathology (composed of hyperphosphorylated Tau tangles) and synaptic loss. in vivo studies linking Tau pathology and mitochondrial alterations at the synapse, an avenue that could lead to synaptic loss, remain predominantly scarce.

Parkinson's disease relevant pathological features are manifested in male Pink1/Parkin deficient rats.

Animal disease models are important for neuroscience experimentation and in the study of neurodegenerative disorders. The major neurodegenerative disorder leading to motor impairments is Parkinson's disease (PD). The identification of hereditary forms of PD uncovered gene mutations and variants, such as loss-of-function mutations in PTEN-induced putative kinase 1 (Pink1) and the E3 ubiquitin ligase Parkin, two proteins involved in mitochondrial quality control, that could be harnessed to create animal models.