Degen Regen References

OEC rat thoracic spinal transections

Rat CST lesion OEC transplant, cells do not pass scar but functional recovery

OEC injections dogs w contusive spinal cord injury--> increased hindlimb coordination but no long tract improvement

Paralysed man regained some function post OEC transplant

Antibodies versus TGFbeta1,2 decreases astrocytic response

Ablation of astrocytes in mice increased oedema, leukocyte recruitment, BBB permeability and neuronal loss v WT

STAT3 selective KO mice

Rho inhibition--> neurite extension to previously inhibitory stripes, CSPG inhibition usually leads to Rho-mediated growth cone collapse

Intrathecal ChABC injections increased fibres crossing a lesion (cats)

ChABC increased sprouting (rat sensorimotor cortex), very limited regeneration

Rolipram (PDE IV inhibitor) reduced astrocyte activation, enhanced serotenergic fibre regeneration.

Cells overexpressing alpha synuclein have defective exocytosis

Alpha synuclein KO mice have greater vesicle availability

Alpha synuclein enhances DAT transport to the membrane

Increased VMAT2 when alpha-synuclein is knocked down

Cells overexpressing alpha synuclein have impaired chaperone-mediated autophagy; Rab localisation is massively altered in yeast overexpressing alpha synuclein

Alpha synuclein increases mitochondrial fragmentation

Parkin mutations, Pink1 mutations decrease number of DAergic neurons in the brain; the expression of parkin rescued both phenotypes

DJ-1 mutation causes mitochondrial dysfunction, DJ-1 expression can rescue Pink1 mutants

LRRK2 is specifically localised in lysosomal-autophagic organelles; knockdown of LRRK2 increases LC-III turnover and autophagy

hESC derived DAergic midbrain neurons implanted to mouse PD model, MPTP-lesioned Rhesus monkeys

iPSCs succesfully converted from fibroblasts into midbrain neurons

Greater Abeta42 deposition in ApoE homozygotes; also increased plaque binding (PET)

Induced KO of ApoE in hippocampus reduced insoluble Abeta42 by 50% in hAPP mice

Very little degeneration of Tau KO hippocampal neurons when cultured in Abeta (versus WT)

Abeta activates NMDARs, which can be partially blocked by subunit antagonism

There is very little neuroanatomical or temporal correlation between plaques and degen.

Abeta oligomers cause neuron death

There is a strong positive correlation between Abeta oligomers and Tau pathology

Accumulation of autophagosomes in neurons from AD brains

Less acidity of lysosomes in presenelin KO mice

ApoE epsilon4 expression increased lysosomal leakage compared to ApoE epsilon3

Inhibition of lysosomal proteolysis led to accumulation of electron-dense autophagosomes

Deletion of lysosomal cathepsin inhibitor in hAPP mice decreased e.c. amyloid, giant autolysosomes and caused behavioural improvements

iPSCs from AD patients can be used to screen drugs, the subsequent neurons had increased Abeta secretion, phosphorylated Tau and activated GSK-3beta

mAb versus ApoE reduced Abeta plaque load in hAPP mice, also recruited microglia

Intracerebroventricular injection of Abs versus IL-12,IL-23 (microglial cytokines) decreased amyloid in hAPP mice and improved cognition