Impairment of microtubule-dependent trafficking by overexpression of alpha-synuclein.

Abnormal accumulation of alpha-synuclein (alpha-syn) has been linked to several neurological disorders, including Parkinson's disease (PD). However, the underlying mechanism by which alpha-syn accumulation affects neuronal function and survival remains unknown. Here, we provide data suggesting a possible effect of aggregated alpha-syn on the microtubule (MT) network.

Clearance of alpha-synuclein oligomeric intermediates via the lysosomal degradation pathway.

Cytoplasmic deposition of alpha-synuclein aggregates is a common pathological feature of many neurodegenerative diseases. Strong evidence for the causative role of alpha-synuclein in these disorders is provided by genetic linkage between this gene and familial Parkinson's disease and by neurodegeneration in transgenic animals that overexpress this protein. In particular, it has been hypothesized that the accumulation of nonfibrillar oligomers of alpha-synuclein, which serve as intermediates for fibrillar inclusion body formation, causes neurodegeneration.

Delta 9-tetrahydrocannabinol disrupts mitochondrial function and cell energetics.

We have observed rapid and extensive depletion of cellular energy stores by Delta(9)-tetrahydrocannabinol (THC) in the pulmonary transformed cell line A549. ATP levels declined dose dependently with an IC(50) of 7.5 microg/ml of THC after 24-h exposure.