Athanasios AlexandrisJohns Hopkins Medicine | JHUSOM · Department of Pathology
Athanasios Alexandris
MBChB, iBSc
Also find me at @a_alexandris (twitter)
About
19
Publications
4,826
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244
Citations
Introduction
I am a postdoctoral research fellow in the division of Neuropathology at Johns Hopkins (Dr Koliatsos Lab) with main focus of research on the neurodegenerative mechanisms associated with traumatic brain injury with a particular focus on axonal degeneration. Other research interests include the neuropathology of Lewy body disorders and Alzheimer's disease.
Additional affiliations
September 2018 - present
August 2016 - August 2018
Position
- Fellow
Description
- Worked on independent projects under the supervision of Prof. Johannes Attems (Neuropathology of the cholinergic system in LBD and AD) and Dr Chris Morris (Expression and perturbation of LAG3 in LBD).
Education
September 2013 - May 2014
Independent Researcher
Field of study
- Neuroscience
September 2010 - May 2016
Publications
Publications (19)
Wallerian degeneration (WD) is a conserved axonal self-destruction program implicated in several neurological diseases. WD is driven by the degradation of the NAD+ synthesizing enzyme NMNAT2, the buildup of its substrate NMN, and the activation of the NAD+ degrading SARM1, eventually leading to axonal fragmentation. The regulation and amenability o...
Traumatic axonal injury (TAI) and the associated axonopathy are common consequences of traumatic brain injury (TBI), contributing to significant neurological impairments following TBI. It has been previously suggested that TAI activates a highly conserved program of axonal self-destruction known as Wallerian degeneration (WD). In the present study,...
Traumatic axonal injury (TAI), thought to be caused by rotational acceleration of the head, is a prevalent neuropathology in traumatic brain injury (TBI). TAI in the optic nerve is a common finding in multiple blunt-force TBI models, and hence a great model to study mechanisms and treatments for TAI, especially in view of the compartmentalized anat...
Traumatic brain injury (TBI) after high-energy, behind helmet blunt trauma (BHBT) is an important but poorly understood clinical entity often associated with apnea and death in humans. In this study, we use a swine model of high-energy BHBT to characterize key neuropathologies and their association with acute respiratory decompensation. Animals wit...
Significance:
The remarkable geometry of the axon exposes it to unique challenges for survival and maintenance . Axonal degeneration is a feature of peripheral neuropathies, glaucoma, and traumatic brain injury, and an early event in neurodegenerative diseases. Since the discovery of Wallerian degeneration (WD), a molecular program that hijacks NA...
White matter pathology is common across a wide spectrum of neurological diseases. Characterizing this pathology is important for both a mechanistic understanding of neurological diseases as well as for the development of neuroimaging biomarkers. Although axonal calibers can vary by orders of magnitude, they are tightly regulated and related to neur...
Nemo-like kinase (NLK), an evolutionarily conserved serine/threonine kinase, is highly expressed in the brain, but its function in the adult brain remains not well understood. In this study, we identify NLK as an interactor of huntingtin protein (HTT). We report that NLK levels are significantly decreased in HD human brain and HD models. Importantl...
Background:
Traumatic brain injury (TBI) is a major cause of CNS neurodegeneration and has no disease-altering therapies. It is commonly associated with a specific type of biomechanical disruption of the axon called traumatic axonal injury (TAI), which often leads to axonal and sometimes perikaryal degeneration of CNS neurons. We have previously u...
Optogenetically engineered human neural progenitors (hNPs) are viewed as promising tools in regenerative neuroscience because they allow the testing of the ability of hNPs to integrate within nervous system of an appropriate host not only structurally, but also functionally based on the responses of their differentiated progenies to light. Here, we...
Aims:
Galanin is a highly inducible neuroprotective neuropeptide and in Alzheimer's disease (AD), a network of galaninergic fibres has been reported to hypertrophy and hyperinnervate the surviving cholinergic neurons in the basal forebrain. We aimed to determine a) the extent of galanin hyperinnervation in patients with AD and Lewy body disease an...
Post-translational modifications (PTMs) of proteins regulate various cellular processes. PTMs of polyglutamine-expanded huntingtin (Htt) protein, which causes Huntington's disease (HD), are likely modulators of HD pathogenesis. Previous studies have identified and characterized several PTMs on exogenously expressed Htt fragments, but none of them w...
Introduction
The degeneration of the basal cholinergic neurons in the basal forebrain and particularly in the nucleus basalis of Meynert (nbM) is a key neuropathological correlate of cognitive decline in dementing diseases like Alzheimer's disease (AD) and Lewy body disorders (LBD) i.e. Parkinson's disease (PD), Parkinson's disease dementia (PDD) a...
Introduction
Depletion of cholinergic neurons within the nucleus basalis of Meynert (nbM) is thought to contribute to the development of cognitive impairments in both Alzheimer’s disease (AD) and Lewy body disorders (LBD). It has been reported that, in late stage AD, a network of fibres that contain the neuropeptide galanin displays significant hy...
Introduction: Galanin is a highly inducible, pleiotropic neuropeptide that modulates several neurotransmitter systems including the cholinergic neurons of the nucleus basalis of Meynert (nbM). These neurons are severely depleted in Parkinson’s disease (PD), PD dementia (PDD), dementia with Lewy bodies (DLB) and Alzheimer’s disease (AD). The resulta...
Gambling is a recreational activity observed across most cultures, yet for about 2% of the general population , and becomes significantly disordered and interferes with life functioning. This condition, long conceptualized as an impulse control disorder (DSM-IV, ICD-10) is increasingly recognized as a be-havioral addiction akin to substance use dis...
Introduction
Depletion of cholinergic neurons within the nucleus basalis of Meynert (nbM) is thought to contribute to the development of cognitive impairments in both Alzheimer’s disease (AD) and Lewy body disorders (LBD). It has been reported that, in late stage AD, a network of fibres that contain the neuropeptide galanin displays significant hyp...
Questions
Questions (2)
I would like to create an AAV vector containing 3 gRNAs with their promoters and a fluorescent marker so that it can be packaged in a single virus for an in vivo experiment. I have contacted several biotech companies and although in theory it is totally possible (e.g. golden gate assembly) and people have actually been doing this, it has been difficult to find a company that can provide this service. Unfortunately, we don’t have this expertise in our lab at the moment. I was wondering if anyone would have any ideas regarding possible options.
I wish to investigate with WB a transmembrane protein which is localised in endosomes/lysosomes and the synaptic membrane. I particular I would like to find the most appropriate method to isolate the synaptic membrane and lysosomal/endosomal membranes from brain homogenates in order to measure the relative abundances of that protein in each fraction. Thank you in advance.
