PD could be (I'd even dare say probably) a prion disease:
Is Parkinson’s disease a prion disorder?
microbiologybytes.com
In PNAS, Warren Olanowa and Stanley Prusiner ask, Is Parkinson’s disease a prion disorder?
Parkinson’s disease (PD) is an age-related, neurodegenerative disease that affects approximately one million people in the United States. Pathologically, the disease is characterized by a loss of dopamine neurons in the substantia nigra coupled with proteinaceous inclusions in nerve cells and terminals, known as Lewy bodies and Lewy neurites, respectively. PD pathology is also known to affect nondopamine neurons in the upper and lower brainstem, olfactory system, cerebral hemisphere, spinal cord, and autonomic nervous system. The cause of cell death in PD is not known, but proteolytic stress with the accumulation of misfolded proteins has been implicated.
In the current issue of PNAS, Desplats et al demonstrate that nerve cells which overexpress tagged alpha-synuclein can transmit the protein to neural stem cells in both in vitro and in vivo models (Inclusion formation and neuronal cell death through neuron-to-neuron transmission of alpha-synuclein. 2009 PNAS USA 106:13004–13005). This important study could explain the remarkable finding that human embryonic dopamine nerve cells implanted into the striatum of patients with PD develop PD pathology with loss of dopamine markers and classic Lewy bodies. It also provides insight into how alpha-synuclein pathology might sequentially spread throughout the nervous system in PD.
It is thus possible that PD is a prion disorder resulting from increased production and/or impaired clearance of proteins such as alpha--synuclein, leading to misfolding and the formation of toxic oligomers, aggregates, and cell death. Further, it is possible that alpha-synuclein is a prion protein that can self-aggregate and be transmitted to unaffected cells, thus extending the disease process. While genetic causes represent an obvious source of increased levels of aberrantly folded alpha-synuclein in familial PD cases, a combination of aging, oxidative stress, inflammation, environmental toxins, hereditary factors, and impaired clearance may all feature in varying ways in causing altered metabolism of alpha-synuclein, resulting in the pathogenesis of sporadic PD. This concept suggests that drugs directed toward reducing the formation and/or facilitating the clearance of misfolded alpha-synuclein, so as to arrest or reverse the self-propagation process, might represent a novel therapeutic interventions for the treatment of PD.
Original paper:
pnas.org |
