So far, this has been a great year for HD research. In my opinion the interaction between mutant huntingtin and innate immunity is the key to understanding HD. Some researchers now seem to be focusing on this fertile ground.

Researchers are some of the smartest people on earth. The challenge of HD has attracted the most brilliant of all. They only need to look in the right place to conquer the killer Huntington's disease. --Jerry 07/25/00
Adapted from:Immunopharmacology 2000 Aug 1;49(1-2):171-186; Gasque P, et al.

The innate immune system and notably the complement (C) system play important roles in host defense to recognise and kill deleterious invaders or toxic entities, but activation at inappropriate sites or to an excessive degree can cause severe tissue damage.

C has been implicated as a factor in the exacerbation and propagation of tissue injury in numerous diseases including neurodegenerative disorders.

In this article, we review the evidence indicating that brain cells can synthesise a full lytic C system and also express specific C inhibitors (to protect from C activation and C lysis) and C receptors (involved in cell activation, chemotaxis and phagocytosis).

We also summarise the mechanisms involved in the antibody-independent activation of the classical pathway of C in Alzheimer's disease, Huntington's disease and Pick's disease. Although the primary role of C activation on a target cell is to induce cell lysis (particularly of neurons), we present evidence indicating that C (C3a, C5a, sublytic level of C5b-9) may also be involved in pro- as well as anti-inflammatory activities.

Moreover, we discuss evidence suggesting that local C activation may contribute to tissue remodelling activities during repair in the CNS