Nerve pathway for combating axon injury and stress may hold benefits for individuals with neurodegenerative disorders

Neurons expressing a toxic form of spinocerebellar ataxia type 3 (SCA3) with protective pathway enabled (left) and blocked (right). Credit: Melissa Rolls.

(Medical Xpress) -- Researchers from the Huck Institutes' Center for Cellular Dynamics — led by Center director Melissa Rolls — have found that a neuroprotective pathway initiated in response to injured or stressed neural axons serves to stabilize and protect the nerve cell against further degeneration.

Neurons, or nerve cells, typically have a single axon that transmits signals to other neurons or to output cells such as muscle tissue, and as these axons extend for long distances within the cell, they are thus at risk for injury.

Furthermore — if an axon is damaged, its parent neuron can no longer function; and since many animals develop only one set of neurons, those neurons will mount major responses to axon injury.

"Neurons are quite remarkable cells," says Dr. Rolls. "Most of them need to survive and function for your entire lifetime. Maybe then it shouldn’t be a surprise that they do not give up easily when damaged or stressed, but it is amazing to be able to watch them fight back and stabilize themselves."

Dissecting Drosophila

Dr. Rolls and her team set out to understand these cellular responses to axon injury by observing the effects of severing fruit fly axons with a laser.

What they found was that the neurons responded to the injury by increasing production of microtubules — cytoskeletal components responsible for maintaining cell structure and providing platforms for intracellular transport — in order to stabilize the neural dendrites, which are the branched structures responsible for transmitting signals to the nerve cell body.

In addition to acute injury response, the team also investigated neurons' response to long-term axon stress — and found similar results.

This video is not supported by your browser at this time.

This video shows the difference in microtubule dynamics between cells expressing a non-toxic form of the huntingtin protein (left) and cells expressing a disease-causing form (right).

Accumulation of misfolded proteins or protein aggregates — responsible for neurodegenerative diseases such as Huntington's disease and spinocerebellar ataxia — induced the same type of cytoskeletal changes as acute axon injury.

Dr. Rolls elaborates: "The assays that we use are all in vivo, so we can literally watch what the neurons do in different scenarios, including cutting of their axon. Being able to observe the cellular responses gave us some ideas we would not have come up with otherwise. For example, it is not intuitive that expressing a protein that causes degeneration would trigger the cell to turn on a pathway that delays degeneration."

Conclusions and implications

Based on their observations, the authors suggest that this pathway represents an endogenous neuroprotective response to axon stress — and could potentially be developed into a diagnostic tool for the detection of early stages of neurodegenerative disease, or even utilized in novel therapies for such illnesses.

"We don't yet know if all types of neurodegenerative disease trigger this type of stabilization pathway; but if there are some diseases in which it is off, then it may be beneficial to try to turn it on to help the neurons resist degeneration," says Dr. Rolls.

The results of the study have been published in Proceedings of the National Academy of Sciences.

Provided by Pennsylvania State University

"Nerve pathway for combating axon injury and stress may hold benefits for individuals with neurodegenerative disorders." June 27th, 2012.http://medicalxpress.com/news/2012-06-nerve-pathway-combating-axon-injury.html

Posted by
Robert Karl Stonjek

Beautiful Plains

SEVEN TIPS TO IMPRESS THE CEO

7 Rules for Meetings With Top Execs

Executives are busy people. So once you’ve gotten onto the calendar, make the most of the opportunity.

Congratulations! You’ve finally landed a one-on-one meeting with a top exec, a powerful player inside your customer’s firm.  It’s a great opportunity, but you’ve got to be certain to take advantage of it.

Make sure you follow these simple steps.

1. Do your research.

Before the meeting, research and review the exec’s “business agenda”–what he or she needs to accomplish organizationally.  Then use your contacts in the firm and your own business acumen to understand the exec’s “personal agenda”–likely career goals, the job that he or she is angling for, and so forth.

2. Don’t assume the exec knows who you are.

Busy execs are often unaware (or can’t remember) why a particular meeting is on their agenda. Introduce yourself and explain why you’re there, tying the subject matter to both the business agenda and, more subtly, the personal agenda of the executive in question.  For example: “I’m John Doe from Acme and I’m here to discuss how to increase profitability through improvements in quality control.”

3. Establish credibility immediately.

Within the first few minutes, demonstrate that you’ve done your homework and understand the company, its challenges and its place in its industry.  Focus on business issues that the executive faces–never the specific bells and whistles on your product.  Execs don’t care about features and functions; they want to know how you’re going to change the bottom line.

4. Ask intelligent questions.

Frame everything according to the drivers that affect the business and the metrics that this exec uses to evaluate activities.  For example, if you're talking to a CFO, you might ask questions about the ROI expectations that the firm uses to make purchasing decisions. If you're talking to a chief technology officer, you might ask questions about the how the rest of the company measures IT performance.

5. Listen more than you talk.

Once you've asked a question, hear what the exec has to say. A productive conversation with a customer is one in which the customer does most of the talking.  Your job is to guide the conversation so that you discover what you need to know in order to be of service to that customer. You need to fully understand a company's problem before proposing a solution.

6. Add value to the conversation.

Resist the temptation to present your solution right then and there.  Anything resembling a sales pitch will make it seem as if your haven't been listening or (worse) don't care about what the exec just told you.  Instead, bring additional value to the conversation by introducing a different business perspective and your experience dealing with similar problems.

7. Close on a next step.

Involve the exec directly in planning any subsequent actions concerning your offering. In most cases, this will involve an opportunity for you to present some kind of customized solution to the problems you've been discussing. However, take the exec's lead on how to go about this.  Ideally, you want the executive to make some kind of public commitment to the project, even if it's just to schedule a group meeting to discuss the idea further.

The above is based on several sources, but draws heavily on a conversation with Dr. Steve Bistritz and Nicholas A.C. Read, authors of the bestselling book Selling to the C-Suite.